Cytogenetic Analysis in

Hematological Malignancies

Hwei-Fang Tien, National Taiwan University Hospital

Recurrent chromosomal abnormalities in Hematological malignancies

Abnormalities important for classification 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 -Y, del(11q); del(5q), del(12p), del(20q); del(7q), +8, +19, i(17q); -7, inv(3)

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)

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

Case Demonstration

Diagnosis

BM smears in a patient with thrombocytopenia and anemia

NTUH, Gene Chromosome Cancer, 1995,12:161

Cytogenetic Abnormalities

NTUH, Gene Chromosome Cancer, 1995,12:161Final dignosis: hepatosplenic Tγ/δ lymphoma

Large granular lymphocytosis

Br J Haematol, 1998, 103:1124

Cytogenetic Abnormalities

Diagnosis: NK-cell large granular lymphocyte leukemia

PB smears

BM aspirate smears from a patient with pancytopenia

Hypoplastic MDS

Name: 林 X 榮 , 46, XY, -7 [20]

Chromosomal abnormality

Diagnosis: hypoplastic MDSLeukemia, 2008, 22:544

Case Demonstration

For Lymphoma Staging

BM study for staging in a patients with DLBCL

BM biopsy: no lymphoma involvement

BM smears

Same Clonal Chromosomal Abnormalities in Lymph Node as in Bone Marrow

Lymph node Bone marrow

Lymphoma involvement of BM is confirmed

Risk Stratification

Impact of Cytogenetics in AML 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

Cytogenetic Scoring System in MDS (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

Blood. 2007;109:3489

Prognostic relevance of chromosome aberrations in CLL

Best Pract Res Clin Haematol. 2007 20:439

17p-

11q-

+12

13q- sole

normal

Follow Up the Clinical Course

Chronic Myeloid Leukemia, Chronic Phase

CML in acute transformation

Indication of Cytogenetic Study

• Unknown cause of cytopenia• Fever of unknown origin• WHO classification of AML and ALL• MDS diagnosis, 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 )