Cytogenetics Flashcards
Gene of t(9;22) with variable breakpoint
BCR Major breakpoint 22q11.2 (CML) 210kd Exons 12-14 Minor breakpoint 22q11.1 (ALL) 190 kd Exons (1-2) micro breakpoint
% of CML and ALL with cryptic BCR-ABL
CML 5%
ALL rare
Critical deleted region in del(5q) syndrome
1.5Mb at 5q31.2
EGR1 gene
Clinical syndrome assd with del(5q)
female predominant
refractory macrocytic anemia
hypolobulated micromegakaryocytic hyperplasia
indolent course
location of TP53
17p13.1
In children monosomy 7 as sole abnormality is assd with
MDS
JMML
trisomy 8 is seen in ____ and is found in over 10% of ___
all myeloid neoplasms
MDS
del(17p) often seen in ___
MDS as part of a complex karyotype
AML and RAEB
frequently therapy-related
common cytogenetic abnormalities seenin classic MPNs
gain (1q)
+8, +9
del(13q)
del(20q)
3 most common abnormalities in PV
+8
+9
del(20q)
3 most common abnormalities in PMF
+8
13q-
del(20q)
4 most common abnormalities in ET
+1q
+8, +9
del(20q)
most common abnormality in systemic mastocytosis
4q12 rearrangements (KIT)
p230 BCR-ABL fusion protein found in:
neutrophilic CML
most common additional abnormalities in CML (4)
+Ph
+8
i(17q)
+19
details of JAK2 mutation
mutation at codon 617 of JAK2 (9p24.1)
phenylalanine for valine substitution (V617F)
other mutations seen in JAK2 neg PV patients
MPL
TET2
CBL
most common abnormalities in PV progression (3)
del(5q)
del(7p)
del(17p)
4-5% of patients with ET have mutations of
MPL
Most common abnormality in CEL with PDGFRA
deletion of CHIC2 at 4q12
leading to FIP1L1-PDGFRA fusion
most common mutation in systemic mastocytosis
KIT 4q12 mutation D816V
leads to relative resistance to Gleevec
there is an association of systemic mastocytosis with what AML?
core binding factor AMLs
t(8;21) and inv(16)
location of PDGFRA
4q12
location of PDGFRB
5q33
location of FGFR1
8p12
most common translocation involving PDGFRA
t(4;12) PDGFRA-ETV6
most common translocation involving PDGFRB
t(5;12) PDGFRB-ETV6
most common translocation involving FGFR1
t(8;13) FGFR1-FLT3
translocations involving PDGFRA and PDGFRB are associated with responsiveness to ____
tyrosine kinase inhibitors
a rearrangement involivng a tyrosine kinase that is associated with T-cell lymphoma
t(5;9) ITK-SYK
6 genes that code for tyrosine kinases that are frequently seen in rearrangements
ABL1 (9q34) ABL2 (1q25) FLT3 (13q12.2) SYK (9q22) JAK2 (9q24) NTRK3 (15q25.3)
7 transcription factors commonly mutated in MDS/MPN
CEBPA - 19q NPM1 - 5q WT1 - 11p TET2 - 4q RUNX1 - 21q ASXL1 - 20q CBL - 11q
2 most common mutations in JMML
-7/del(7q)
del(5q)
what will worsen the favorable prognosis of AML with t(8;21)?
KIT mutation
what type of AML has highest risk of CNS involvement
inv(16)
“clue” to presence of inv(16) by cytogenetics
+22
variant PML translocation that does not respond to ATRA
t(11;17) ZBTB16(PLZF)-RARA
variant PML transolation that does respond to ATRA
t(5;17) NPM1-RARA
details about AML with t(9;11)
monoctic/myelomonocytic phenotype
CD34 negative
frequent RAS mutations
AML with basophilia
t(6;9) DEK-NUP214
With normal karyotype, these abnormalities alone show good prognosis in AML
NPM1
CEBPA
With normal karyotype, these mutations have unfavorable outcome in AML
FLT3
KMT2A
Other mutation seen in AML with translocations involving core binding factor genes [ t(8;21), inv(16)]
KIT
Most common karyotypic finding in blastic plasmacytoid dendritic cell neoplasm
complex karyotype
Two recurrent genetic abnormalities seen in mixed phenotype acute leukemia
t(9;22)
KMT2A rearrangements
additional abnormality in Ph+ ALL that gives much worse prognosis
minus 7
Additional cytogenetic abnormalities commonly seen in CML and ALL
+8
+Ph
clues to the presence of KMT2A(MLL) rearrangement in ALL
CD10- immunophenotype
high WBC
<1 yr old
Importance of t(1;19)
seen in ALL
generally poor prognosis
Chromosomes preferentially lost in hypodiploid ALL
3, 7, 15, 17
