1. Cytogenetic Analysis in
Hematological Malignancies
Hwei-Fang Tien, National Taiwan
University Hospital

2. 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.

3. 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

4. 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)

5. Case Demonstration
Diagnosis

6. 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

7. BM smears

8. 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

9. NK-cell large granular lymphocytosis
NTUH, Br J Haematol, 1998, 103:1124
Cytogenetic Abnormalities
Diagnosis: NK-cell large granular lymphocyte leukemia
PB smears

10. Differential diagnosis of hypoplastic MDS with AA
BM smears

11. Name: 林X榮,
46, XY, -7 [20]
Chromosomal abnormality
Diagnosis: hypoplastic MDS
NTUH, Leukemia, 2008, 22:544

12. Case Demonstration
For Lymphoma Staging

13. BM study for staging in a patients with DLBCL
Pathol exam. of the BM biopsy specimen: no lymphoma involvement
BM smears

14. BM smears

15. Same clonal chromosomal abnormalities
in bone marrow as in lymph node
Lymph node Bone marrow
DLBCL stage IV with BM involvement is confirmed

16. Risk Stratification

17. 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-related
other t(11q23)
t(15;17)
t(8;21)
Inv(16)
5876 patients
Normal

18. MDS: New Cytogenetic Scoring System (n=2,754)
Abnormality Overall
survival
AML
transformation
Prognostic
Subgroup
No.
of
Pts
% 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 other
Independent
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

19. MM: Impact of genomic aberrations on OS
Avet-Loiseau et al, Blood. 2007;109:3489

20. Implication of cytogenetics on survival in MM
overall survival (month)
2001000
CumulativeSurvival
1.0
.8
.6
.4
.2
0.0
Hyperdipolidy (n=19)
Non-hyperdiploid (n=25)
p=0.025
overall survival (month)
2001000
CumulativeSurvival
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

21. overall survival (month)
2001000
1.0
.8
.6
.4
.2
0.0
FISH_∆13 only, N=23
Without abnormality, N=57
p=0.013
CG_∆13
N=8
Survival Analysis:
Combined cytogenetics & FISH
NTUH, Ann Oncol 16:1530, 2005

22. Prognostic relevance of chromosome aberrations in CLL
Zenz & Dohner, Best Pract Res Clin Haematol. 2007 20:439
17p-
11q-
+12
13q- sole
normal

23. Implications of 17p-/11q- on OS in CLL
Cytogenetics
FISH
NTUH, Ann Hema, 2013, in press

24. Follow Up the Clinical Course

25. Chronic Myeloid Leukemia, Chronic Phase

26. CML in blast crisis

27. 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

28. 台灣藍鵲（ Formosan Blue Magpie )

29. 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.

30. Burkitt lymphoma

31. t(8:14)(q24:q32)

32. Relationship between Chromosomal
Alterations 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

33. Hypoplastic MDS