Sekonder Hemofagositik Lenfohistiyositoz’li çocukların ... · Sekonder Hemofagositik...

Sekonder Hemofagositik Lenfohistiyositozrsquoli ccedilocukların plazma mikroRNA profillemesi

Ali Bay Enes Coşkun Serdar Oumlztuzcu Fatih Yilmaz Sercan Erguumln Elif Aktekin

Gaziantep Uumlniversitesi Tıp Fakuumlltesi

Ccedilocuk Hematoloji Kliniği

Amaccedil

bull Bu ccedilalışmada sekonder HLHrsquoli hastaların ve sağlıklı kontrollerin plazmalarında 379 miRNArsquonın ekspresyonu araştırıldı

bull Hasta grubu ile sağlıklı ccedilocukların plazma miRNA ekspresyon seviyelerini kıyaslarak ccedilocukluk ccedilağı sekonder HHLrsquosi iccedilin yeni bir biyomarker belirlemeyi amaccedilladık

bull Bu ccedilalışma literatuumlrde bu konuda yapılan ilk araştırmadır

Giriş

bull Hemofagositik lenfohistiyositoz (HLH) NK huumlcreleri ve sitotoksik T huumlcrelerinin aşırı aktivasyonu sonucunda oluşan nadir ancak ciddi oranda oumlluumlmcuumll olabilen hiperinflamatuar bir hastalıktır

bull HLH kontrolsuumlz ve disfonksiyonel immun yanıtın yol accediltığı bir hastalıktır

1 Bode SF Lehmberg K Maul-Pavicic A et al Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis Arthritis Res Ther 201214213

bull Bilinen genetik mutasyonu bulunmayan ve genetik yatkınlık duumlşuumlnduumlrmeyen HLH tanılı hastalar sekonder HLH olarak sınıflandırılırlar

SEKONDER HLH

bull İnfeksiyonlarla ilişkili (İAHS)

viruumlsler (VAHS)

bakteriler

parazitler

bull Malign hastalıklarla ilişkili (MAHS)

bull Metabolik hastalıklarla

bull İlaccedillarla ilişkili

bull Romatolojik hastalıklarla ilişkili (MAS)

5

6

(1) HLH ile uyumlu molekuumller tanı

(2) Aşağıdaki 8 tanı kriterinden en az 5rsquoinin goumlsterilmesi

bull Ateş

bull Splenomegali

bull Sitopeni (periferik kanda 3 seriden en az 2rsquosinde goumlruumllen)

- Hemoglobin (lt 90 gL) - Trombosit (lt 100 times 109L) - Noumltrofil (lt 10 times 109L)

bull Hipertrigliseridemi veveya hipofibrinojenemi

- Accedillık trigliseridi ge30 mmolL (ge265 mgdl)

- Fibrinojen le15 gL

bull Kemik iliği dalak ya da lenf nodlarında malignite kanıtı olmadan hemofagositozun goumlsterilmesi

bull Ferritin ge 500microgL

bull Duumlşuumlk NK huumlcre aktivitesi

bull Ccediloumlzuumlnebilir CD25 ge 2400 UmL

Tanı 2004 Kriterleri

Mikro RNA

bull Endojen olarak sentezlenen kodlama yapmayan sekansa oumlzguumll biccedilimde hedef gen expresyonunda reguumllasyon yapan 18-22 nukleotid uzunluğunda tek sarmallı RNArsquolardır

bull miRNArsquolar DNArsquodan uzun premiRNA olarak transkripte edildikten sonra Drosha RNAaz III enzimiyle daha kuumlccediluumlk parccedilalara ayrılıp nukleusun dışına taşınırlar

bull pre- miRNA ribonukleaz Dicer tarafından kesilip olgun ccedilift sarmallı miRNA elde edilir

bull Bu olgun miRNArsquodan oluşan tek sarmallı miRNA RNA-induced silencing complex (RISC)rsquo e katılır

bull miRNArsquolar intron genlerinden kodlanırlar

bull RISC hedef mRNArsquonın tranlasyon yapılmamış 3rsquo veya 5rsquo komplementer boumllgesine bağlanıp okunma ccedilerccedileveleri ve promoter boumllgeleri accedilar

bull mRNA kesilmesi veya translasyonel represyon aracılığıyla miRNArsquolar gen ekspresyonun negatif reguumllasyonunu veya upreguumllasyonunu gerccedilekleştirirler

bull Bir gen birccedilok miRNA tarafından reguumlle edilebilir

93 Bartel D P (2004) MicroRNAs Genomics biogenesis mechanism and function Cell 116 281ndash297 94 Hammond S M (2005) Dicing and slicing The core machinery of the RNA interference pathway FEBS Letters 579 5822ndash5829 95 Okamura K Hagen J W Duan H Tyler D M amp Lai E C (2007) The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila Cell 130 89ndash100 96 Ruby J G Jan C H amp Bartel D P (2007) Intronic microRNA precursors that bypass Drosha processing Nature 448 83ndash86 97 Gregory R I Chendrimada T P amp Shiekhattar R MicroRNA biogenesis isolation and characterization of the microprocessor complex Methods Mol Biol 342 33ndash47 (2006) 98 Kloosterman W P Wienholds E Ketting R F amp Plasterk R H Substrate requirements for let 7 function in the developing zebrafish embryo Nucleic Acids Res 32 6284ndash6291 (2004) 99 Lytle J R Yario T A amp Steitz J A Target mRNAs are repressed as efficiently by microRNA binding sites in the 5 UTR as in the 3 UTR Proc Natl Acad Sci USA 104 9667ndash9672 (2007) 100 Lee I et al New class of microRNA targets containing simultaneous 5-UTR and 3-UTR interaction sites Genome Res 19 1175ndash1183 (2009) 101 He L amp Hannon G J MicroRNAs small RNAs with a big role in gene regulation Nat Rev Genet 5 522ndash531 (2004) 102 Bohnsack M T Czaplinski K amp Gorlich D Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs RNA 10 185ndash191 (2004) 103 Vasudevan S Tong Y amp Steitz J A Switching from repression to activation microRNAs can up-regulate translation Science 318 1931ndash1934 (2007)

Cortez M A et al MicroRNAs in body fluidsmdashthe mix of hormones and biomarkers Nat Rev Clin Oncol 8 467ndash477 (2011) published online 7 June 2011 doi101038nrclinonc201176

AEtheridgeet alExtracellularmicroRNAAnewsourceofbiomarkersMutatResFundamMolMech Mutagen (2011)doi101016jmrfmmm201103004

bull İnsan genomunda ccedilok yaygın olarak bulunurlar ndash transkripsiyon ndash huumlcre siklus reguumllasyonu ndash sinyal transduumlksiyonu ndash huumlcre ccediloğalması ndash huumlcre buumlyuumlmesi ndash apoptozis ndash yağ metaboliması ndash noumlrogenezis

bull miRNA regulasyonundaki bir bozukluk otoimmun

kardiyovaskuumller enfeksiyoumlz metabolik noumlrolojik ve onkolojik hastalıklara yol accedilabilir

Hastalar ve Metod

bull Gaziantep Uumlniversitesi Tıp Fakuumlltesi Ccedilocuk hematoloji kliniğininde sekonder HLH tanısı konulan 11 hasta ve yaş ve cins dağılımı benzer olan 11 sağlıklı ccedilocuk ccedilalışmaya alındı

bull HLH Tanısı HLH 2004 tanı kriterlerine goumlre kondu

bull Ccedilalışmaya alınan hastalar HLHrsquonin ana kriterlerinden en az beş tanesini sağlıyordu

bull MiRNA iccedilin kan oumlrnekleri tanı anında tedavi başlanmadan oumlnce alındı

bull Sekonder HLHrsquoli hastaların ve sağlıklı kontrollerin plazmalarında 379 miRNArsquonın ekspresyonu araştırıldı

bull miRNA izolasyonu HLH hastalarından ve kontrollerden tam kan oumlrnekleri EDTArsquolı tuumlplere alındı 4000 rpm de santrifuumlj edildi

bull Sonra miRNArsquoları da iccedileren total RNA plazmadan miRNeasy Mini Kit (Qiagen GmbH Hilden Germany Cat No217004) kullanılarak ekstrakte edildi

bull cDNA konversiyonu İzole edilen RNA oumlrnekleri TaqManmiRNA Reverse Transcription Kit kullanılarak komplementer DNA (cDNA)rsquo ya ccedilevrildi

bull PreAmplifikasyon cDNA oumlrnekleri qRT-PCR reaksyonuna sokulmadan oumlnce TaqManPreAmp Master Mix kullanılarak preamplfiye edildi Preamplifiye edilmiş cDNA oumlrnekleri sonraki işlemler iccedilin -20degC saklandı

bull Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) QRT-PCR reaksyonları (BioMark Fluidigm San Francisco CA) isimli enstruman ile gerccedilekleştirildi

İstatistik metodu

bull miR-34a-5p normalizasyon iccedilin kullanıldı

bull SPSS 14 programı iccedilin dağılımların homojenitesine goumlre Man Whitney U testi ve student t testi kullanıldı plt005 olan değerler anlamlı olarak kabul edildi

Sonuccedillar

bull Bu ccedilalışma 11 HLHrsquoli ve 11 sağlıklı ccedilocuk uumlzerinde yapıldı

bull HLH grubunda 5 erkek 6 kız hasta

bull HLH grubunda ortalama yaş 103plusmn17 ay

bull Kontrol grubunda ortalama yaş 98plusmn37 ay

Table 1 Patientcharacteristics

Patient no 1 2 3 4 5 6 7 8 9 10 11

Gender M F M F F F F M F M M

Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent disease Hepatitis A idiopatic Chronicgra

nulamatous

disease

Brain

abcess due

to TOFF

CRF MDS Brucellosis Thyphoid

fever

CRF İdiopatic Hepatitis A

Detected agent stafilococuc Stafilococu

c

Brucella Styhphi EBV IgM

Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281

Hemophagocytosis Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive

Prolonged fever

Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive

Hepatosplenomegaly Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive

Outcome live live live Live live live Live live Live Live live

Hastaların karakteristikleri


Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus

Brucella Styhphi Ebstein

Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow


Prolonged fever Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive Positive

Hepatosplenomegal

y



Table 2 List of completelyexpressedmiRNAs

Number of patients Mean Std Deviation

miR-34a-5p 22 127378 176340 Housekeeping gene

miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616

Table 3 List of miRNAs that have significant fold change

MiRNA HLH Control Expression

Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055

Anlamlı kat değişimi tespit edilen miRNArsquolar

MiRNA ekspresyon seviyeleri ile yaş cinsiyet eşlik eden hastalık ve laboratuvar değerleri arasındaki korelasyon saptanamadı

Tartışma

HLHrsquode anlamlı ekspresyon değişimi goumlsteren miRNArsquoların hedef aldığı imflamasyonla ilişkili genler (TargetScan ve MiRanda veri tabanlarına goumlre)

Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p

bull miR-205-5p 621 kat artmış olarak bulundu

bull Transkripsyon faktoumlr E2F1 protein sentezinin G1S fazında oumlnemli role sahiptir boumlylelikle huumlcre oumlmruumlnde ve ccediloğalmasında kritik role sahiptir (20)

bull Huumlcre siklusuyla ilişkili protein E2F5 kronik inflamasyonda upreguumlle olmaktadır (22)

bull Bu bağlamda E2F1 ve E2F5 genlerini hedef alan miR 205-5prsquonin artmış ekspresyon seviyesi HLH gelişimi ve progresyonunu etkileyen immun yanıtın yeni keşfedilen reguumllatoumlrleri olarak duumlşuumlnuumllebilir

bull miR-205-5prsquonin hedef proteinleri de E2F1 ve E2F5rsquodir

20 Vara D Bicknell KA Coxon CH et al Inhibition of E2F abrogates the development of cardiac myocyte hypertrophy J Biol Chem 200327821388-94 22 Wu J Pajoohesh-Ganji A Stoica BA et al Delayed expression of cell cycle proteins contributes to astroglialscar formation and chronic inflammation after rat spinalcord contusion J Neuroinflammation 20129169

miR-194-5p


bull Nuumlkleer faktoumlr kappa B(NF-KB) imflamasyonda ve huumlcre oumlmruumlnde rol alan genlerin transkripsyonunun reguumllasyonunda oumlnemli rol oynar

bull PARP-1 and p300 sinerjistik şekilde TNF alfa ve LPSrsquoe yanıt olarak NF-KB genin ekspresyonunu arttırırlar((24)

bull miR-194-5p hedef geni de p300rsquoduumlr

24 Hassa PO Buerki C Lombardi C et al Transcriptional coactivation of nuclear factor-kappaB-dependent gene expression by p300 is regulated by poly (ADP)-ribose polymerase-1 J Biol Chem 200327845145-53

miR-30c-5p

bull miR-30c-5p 9 kat azalmış olarak bulundu

bull MUC17 kolon epitel huumlcrelerinde eksprese olur İmflamatuar ve neoplastik durumlarda ekspresyonu azalır (25)

bull Bizim bulgularımızda MUC17rsquoyi hedef olan miR-30c-5prsquonin HLHrsquoli hastalarda ekspresyonunun azaldığını tespit ettik

25 Senapati S Ho SB Sharma P et al Expression of intestinal MUC17 membrane-bound mucin in inflammatory and neoplastic diseases of the colon J Clin Pathol 201063702ndash707

Son soumlz

bull Biz bu ccedilalışmayla miR-205-5p miR-194-5p ve miR-30c-5prsquonin HLH iccedilin yararlı markerlar olabileceğini goumlsterdik

bull Yeni keşfedilmiş bu biyomarkerlarla diğer tanı youmlntemlerinin kombine kullanımı HLHrsquoli hastalarda hastalığın progresyonunun daha iyi anlaşılmasında yarar sağlayabilir

bull İmflamasyonla ilişkili HLH patogenezinde roluuml olan miRNArsquoların spesifik roluumlnuumln belirlenmesi iccedilin daha buumlyuumlk ve homojen gruplarda ccedilalışmalara ihtiyaccedil vardır

Amaccedil

bull Bu ccedilalışmada sekonder HLHrsquoli hastaların ve sağlıklı kontrollerin plazmalarında 379 miRNArsquonın ekspresyonu araştırıldı

bull Hasta grubu ile sağlıklı ccedilocukların plazma miRNA ekspresyon seviyelerini kıyaslarak ccedilocukluk ccedilağı sekonder HHLrsquosi iccedilin yeni bir biyomarker belirlemeyi amaccedilladık

bull Bu ccedilalışma literatuumlrde bu konuda yapılan ilk araştırmadır

Giriş





SEKONDER HLH


viruumlsler (VAHS)

bakteriler

parazitler





5

6



bull Ateş

bull Splenomegali











Mikro RNA















Hastalar ve Metod











İstatistik metodu



Sonuccedillar






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz




Giriş





SEKONDER HLH


viruumlsler (VAHS)

bakteriler

parazitler





5

6



bull Ateş

bull Splenomegali











Mikro RNA















Hastalar ve Metod











İstatistik metodu



Sonuccedillar






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz





SEKONDER HLH


viruumlsler (VAHS)

bakteriler

parazitler





5

6



bull Ateş

bull Splenomegali











Mikro RNA















Hastalar ve Metod











İstatistik metodu



Sonuccedillar






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz




6



bull Ateş

bull Splenomegali











Mikro RNA















Hastalar ve Metod











İstatistik metodu



Sonuccedillar






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz




Mikro RNA















Hastalar ve Metod











İstatistik metodu



Sonuccedillar






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz














Hastalar ve Metod











İstatistik metodu



Sonuccedillar






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz











İstatistik metodu



Sonuccedillar






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz




Sonuccedillar






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz





Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158


nulamatous

disease

Brain

abcess due

to TOFF


fever



c


Hgb 7 6 74 83 81 9 96 98 54 76 92

WBC 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Plt 96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride 302 245 203 445 92 275 474 188 481 134 189

Fibrinogen 128 110 275 77 327 624 320 213 146 177

Ferritin 38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

Alt 150 120 143 30 71 29 121 96 13 124 56

Ast 399 312 691 179 124 15 169 79 173 163 281


Prolonged fever






Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz





Patient no 1 2 3 4 5 6 7 8 9 10 11


Age (month) 5 27 57 63 91 136 137 149 155 156 158

Concurrent

disease

Hepatiti

s A

idiopati

c

Chronic

granula

matousd

isease

Brain

abcess

due to

TOFF

Chronic

renal

failure

Myelod

ysplasti

c

syndrom

e

Brucello

sis

Thyphoi

d fever

Chronic

renal

failure

İnfectio

us

Mononu

cleosis

Hepatiti

s A

Detected

agent

Staphyl

ococcus

Staphyl

ococcus


Barr

Virus


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz





Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemoglobin

(gdl)

7 6 74 83 81 9 96 98 54 76 92

WBC (mm3) 2200 1600 2400 2900 1800 700 1800 3300 2300 1900 1600

Platelet

(mm3)

96000 88000 74000 21000 54000 61000 98000 50000 18000 46000 39000

Triglyceride

(mgdl)

302 245 203 445 92 275 474 188 481 134 189


Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz





Patient no 1 2 3 4 5 6 7 8 9 10 11

Fibrinogen

(mgdl)

128 110 275 77 327 624 320 213 146 177

Ferritin

(ngml)

38773 4850 9131 24922 27417 3525 12141 3712 40000 5408 10392

ALT (IUL) 150 120 143 30 71 29 121 96 13 124 56

AST (IUL) 399 312 691 179 124 15 169 79 173 163 281


Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz





Patient no 1 2 3 4 5 6 7 8 9 10 11

Hemophagocytosis

in bone marrow



Hepatosplenomegal

y






miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz







miR-205-5p 22 138944 205745

miR-302c-3p 22 126458 282873

miR-483-5p 22 136035 599616



Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz






Fold change P

miR-205-5p 11 11 10000 621 001

miR-194-5p 9 9 8182 16336 0009

miR-30c-5p 7 10 7727 010 003

miR-192-5p 3 6 4091 92602 0043

miR-618 6 3 4091 61035962 0055



Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz





Tartışma


Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz





Targeted gene

miR-205-5p E2F1

miR-194-5p P300

miR-30c-5p MUC17

Tartışma

miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz




miR-205-5p







miR-194-5p






miR-30c-5p





Son soumlz




miR-194-5p






miR-30c-5p





Son soumlz




miR-30c-5p





Son soumlz




Son soumlz




Sekonder Hemofagositik Lenfohistiyositoz’li çocukların ... · Sekonder Hemofagositik...

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Transcript of Sekonder Hemofagositik Lenfohistiyositoz’li çocukların ... · Sekonder Hemofagositik...