cytogenetic analysis in hematological malignancies
TRANSCRIPT
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Cytogenetic Analysis in
Hematological Malignancies
Hwei-Fang Tien, National Taiwan University Hospital
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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.
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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
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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)
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Case Demonstration
Diagnosis
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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
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BM smears
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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
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NK-cell large granular lymphocytosis
NTUH, Br J Haematol, 1998, 103:1124
Cytogenetic Abnormalities
Diagnosis: NK-cell large granular lymphocyte leukemia
PB smears
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Differential diagnosis of hypoplastic MDS with AA
BM smears
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Name: 林 X 榮 , 46, XY, -7 [20]
Chromosomal abnormality
Diagnosis: hypoplastic MDSNTUH, Leukemia, 2008, 22:544
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Case Demonstration
For Lymphoma Staging
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BM study for staging in a patients with DLBCL
Pathol exam. of the BM biopsy specimen: no lymphoma involvement
BM smears
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BM smears
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Same clonal chromosomal abnormalities in bone marrow as in lymph node
Lymph node Bone marrow
DLBCL stage IV with BM involvement is confirmed
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Risk Stratification
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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
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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
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MM: Impact of genomic aberrations on OS
Avet-Loiseau et al, Blood. 2007;109:3489
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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
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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
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Prognostic relevance of chromosome aberrations in CLL
Zenz & Dohner, Best Pract Res Clin Haematol. 2007 20:439
17p-
11q-
+12
13q- sole
normal
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Implications of 17p-/11q- on OS in CLL
Cytogenetics
FISH
NTUH, Ann Hema, 2013, in press
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Follow Up the Clinical Course
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Chronic Myeloid Leukemia, Chronic Phase
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CML in blast crisis
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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
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台灣藍鵲( Formosan Blue Magpie )