Cytogenetic Analysis in Hematological Malignancies
Transcript of Cytogenetic Analysis in Hematological Malignancies
Cytogenetic Analysis in
Hematological Malignancies
Hwei-Fang Tien, National Taiwan University Hospital
Cytogenetics in Hematological Malignancies
• Most patients with hematological malignancies have clonal chromosomal abnormalities.
• Some recurrent chromosomal abnormalities are tumor- and even subtype-specific, so are good for diagnosis and classification.
• The pattern of chromosomal aberrations may predict treatment response and clinical outcome and is good for risk stratification.
• Genes located at the breakpoints of the recurrent abnormalities play an important role in the process of tumorigenesis and can be the target of treatment.
Purpose of Cytogenetic Study in Hematological malignancies
1. Diagnosis and classification
2. Risk stratification
3. Selection of proper treatment
4. Follow-up of the response
Recurrent chromosomal abnormalities in Hematological malignancies
CML t(9;22)
AML t(8;21), t(15;17), inv(16), t(9;11), inv(3), t(6;9), t(1;22), -5/5q-, -7/7q-
ALL t(4;11), t(1;19), t(v;11q23), t(12;21)
MDS -5/del(5q), del(20q); -7/del(7q), +8
Lymphoma DLBCL t(3q27)
Burkitt t(8;14) and variant
Follicular t(14;18)
Mantle cell t(11;14)
Marginal zone t(11;18), t(1;14), t(14;18)
Case Demonstration
Diagnosis
BM smears in a patient with bleeding tendency
NTUH, Gene Chromosome Cancer, 1995,12:161
23Y/O, male , PB plt, 3000/μL; Hb, 9.2 gm/dL; WBC, normal
Plt count increased to 533x103/μL after steroid treatment, but dropped again 1 mo later.
BM smears
BM smears
Cytogenetic Abnormalities
NTUH, Gene Chromosome Cancer, 1995,12:161
The pt received splectomy. Final dignosis: hepatosplenic Tγ/δ lymphoma
A new cytogentc- clinicopathological entity of NHL
NK-cell large granular lymphocytosis
NTUH, Br J Haematol, 1998, 103:1124
Cytogenetic Abnormalities
Diagnosis: NK-cell large granular lymphocyte leukemia
PB smears
Differential diagnosis of hypoplastic MDS with AA
BM smears
Name: 林 X 榮 , 46, XY, -7 [20]
Chromosomal abnormality
Diagnosis: hypoplastic MDSNTUH, Leukemia, 2008, 22:544
Case Demonstration
For Lymphoma Staging
BM study for staging in a patients with DLBCL
Pathol exam. of the BM biopsy specimen: no lymphoma involvement
BM smears
BM smears
Same clonal chromosomal abnormalities in bone marrow as in lymph node
Lymph node Bone marrow
DLBCL stage IV with BM involvement is confirmed
Risk Stratification
AML: Impact of Cytogenetics based on 2008 WHO Classification
Medical Research Council , United Kingdom Blood. 2010;116(3):354 , Blood Rev, 2011; 25:39
t(9;22)-7/7q--5/5q-Inv(3), t(3;3)
t(9;11)t(3;5)t(6;9)MDS-relatedother t(11q23)
t(15;17)
t(8;21)Inv(16)
5876 patients
Normal
MDS: New Cytogenetic Scoring System (n=2,754)
Abnormality Overall survival
AML transformation
Prognostic Subgroup
No. ofPts
% Single Double Cplx Median(months)
Median (months)
Very good 81 2.9 del(11q), -Y ― ―
60.8 NR
Good (reference)
1,809 65.7 Normal, del(5q)del(12p), del(20q)
Including del(5q)
―
48.6 NR
Intermediate 529 19.2 del(7q), +8, i(17q)+19, any otherIndependent clones
Any other ―
26.0 78.0
Poor 148 5.4 Inv(3)/t(3q)/del(3q),-7
Including-7/del(7q)
3 15.8 21.0
Very poor 187 6.8 ― ― > 3 5.9 8.2
Abbreviations: AML, acute myeloid leukemia; NR, not reached.
Schanz et al, J Clin Oncol, 2012
MM: Impact of genomic aberrations on OS
Avet-Loiseau et al, Blood. 2007;109:3489
Implication of cytogenetics on survival in MM
overall survival (month)
2001000
Cum
ulat
ive
Sur
viva
l
1.0
.8
.6
.4
.2
0.0
Hyperdipolidy (n=19)
Non-hyperdiploid (n=25)
p=0.025
overall survival (month)2001000
Cum
ulati
ve S
urvi
val
1.0
.8
.6
.4
.2
0.0
Normal karyotype (n=106)
Abnormal karyotype (n=44)
P=0.029
NTUH, Ann Oncol 16:1530, 2005
overall survival (month)
2001000
Cum
ulat
ive
Sur
viva
l
1.0
.8
.6
.4
.2
0.0
FISH_∆13 only, N=23
Without abnormality, N=57
p=0.013
CG_∆13N=8
Survival Analysis:
Combined cytogenetics & FISH
NTUH, Ann Oncol 16:1530, 2005
Prognostic relevance of chromosome aberrations in CLL
Zenz & Dohner, Best Pract Res Clin Haematol. 2007 20:439
17p-
11q-
+12
13q- sole
normal
Implications of 17p-/11q- on OS in CLL
Cytogenetics
FISH
NTUH, Ann Hema, 2013, in press
Follow Up the Clinical Course
Chronic Myeloid Leukemia, Chronic Phase
CML in blast crisis
Indication of Cytogenetic Study
• Unknown cause of cytopenia• Fever of unknown origin• WHO classification of AML and ALL• MDS diagnosis and classification (IPSS, IPSS-R)• Lymphoma diagnosis, classification and
staging work up• Risk stratification of CLL and MM• Follow-up of treatment response
台灣藍鵲( Formosan Blue Magpie )
Cytogenetics in Hematological Malignancies
• Most patients with hematological malignancies have clonal chromosomal abnormalities.
• Some recurrent chromosomal abnormalities are tumor- and even subtype-specific, so are good for diagnosis and classification.
• The pattern of chromosomal aberrations may predict treatment response and clinical outcome and is good for risk stratification.
• Genes located at the breakpoints of the recurrent abnormalities play an integral role in the process of tumorigenesis.
Burkitt lymphoma
t(8:14)(q24:q32)
Relationship between ChromosomalAlterations and Pathogenesis of Cancer
Nonrandom nature of chromosomal alterations in cancer CML : t(9;22) AML : t(8;21), t(15;17), inv(16) ALL : t(4;11), t(1;19) Lymphoma : t(8;14), t(14;18), t(11;14)
Constitutional chromosomal deletions predispose to the development of cancer 13q14 deletion retinoblastoma 11p13 or 11p15 Wilms’ tumor
Hypoplastic MDS