This document discusses the importance of cytogenetic analysis in hematological malignancies. It notes that chromosomal abnormalities are common in many hematological cancers and can be used for diagnosis, classification, risk stratification, and treatment selection. Specific recurrent abnormalities are described for cancers like CML, AML, ALL, MDS, and lymphomas. Examples are given showing how cytogenetics can confirm diagnoses, provide prognostic information, and be used to monitor treatment response over time. Cytogenetic analysis is an important tool for understanding and managing many types of blood cancers.
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)
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
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
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
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
