wbc disorders cytogenetics

Question 1

cytogenetics of ALL

Answer 1

hyperploidy (m/c, more than 50 chr)
translocations: t(12;21) (TEL-AML1), t(9;22), t(4;11)
T-ALL: NOTCH1 gain-of-function
B-ALL: loss-of-fxn PAX5, E2A, EBF

Question 2

cytogenetics of AML

Answer 2

de novo: t(8;21), inv(16), or t(15;17)
AML-MDS or tx-AML: deletion/monosomy 5 or 7, MLL gene t(11)
elderly: deletion 5 or 7

Question 3

mechanism of t(8;21) and inv(16)

Answer 3

in AML
encode CBF1a and b that make a TF. Mutation –> dominant negative activity, blocking terminal differentiation.
*Not sufficient alone to cause AML, good prognosis

Question 4

t(15;17)

Answer 4

common translocation in M3 AML (promyelocytic) producing PML/RARa fusion repressor of transcription = halts differentiation
tx: retinoic acid

Question 5

cytogenetics of myelodysplastic syndromes

Answer 5

monosomy 5 or 7
deletions 5q or 7q
trisomy 8
deletions 20q

Question 6

cytogenetics of CLL/SLL

Answer 6

*translocations rare
deletions: 13q (m/c, favorable), 11q (ATM), 17p (p53)
trisomy 12q
somatically hypermutated Ig genes
ZAP70 (worst prognosis)

Question 7

cytogenetics CML

Answer 7

BCR-ABL fusion from t(9;22)

Question 8

cytogenetics polycythemia vera

Answer 8

JAK2 point mutation -> constitutively active kinase

Question 9

cytogenetics essential thrombocythemia

Answer 9

JAK2 or MPL point mutation -> constitutively active kinase

Question 10

cytogenetics primary myelofibrosis

Answer 10

JAK2 or MPL point mutation -> constitutively active kinase

Question 11

cytogenetics B-cell PLL

Answer 11

blastic: t(11;14)
del: 17p, 11q, 13q
MYC translocations, overexpression

Question 12

cytogenetics follicular lymphoma

Answer 12

t(14;18) BCL2-IgH promoter fusion

Question 13

cytogenetics hairy cell leukemia

Answer 13

no consistent karyotypic abnormality

Question 14

cytogenetics marginal zone lymphoma

Answer 14

heterogenous, depends on site

Question 15

cytogenetics DLBCL

Answer 15

25%: t(14;18)
BCL6 rearrangements (chr 3)
t(8;14) - deregulation of MYC
mutations and deletions of p53

Question 16

cytogenetics mantle cell lymphoma

Answer 16

t(11;14) promoter exchange is most common –> Ig-promoter-BCL1 gene –> overexpressed cyclin D

Question 17

cytogenetics Burkitt’s lymphoma

Answer 17

t(8;14), t(2;8), t(8;22) - C-MYC (8) by Ig heavy or light-chain gene

Question 18

cytogenetics anaplastic large cell lympohoma

Answer 18

t(2;5) ALK1 fusion common (TK and nucleophosmin)

Question 19

B-ALL markers

Answer 19

TdT (pre-B or pre-T)
CD19, CD22, PAX5
late pre-B: CD10, CD20, IgM heavy chain; *no surface Igs

Question 20

T-ALL markers

Answer 20

TdT (pre-B or pre-T)
CD1, CD2, CD5, CD7
late pre-T: CD3, CD4, CD8

Question 21

AML markers

Answer 21

myeloperoxidase
immature/multipotent stem cell: CD34
myeloid: CD13, CD33
mature myeloid: CD64, CD15
monocyte: CD14

Question 22

CLL/SLL markers

Answer 22

B-cell markers: CD19, 20, 22
B/T marker: CD23, CD5
low level surface Ig (IgM +/- IgD heavy chains and K or L light chain)

Question 23

hairy cell leukemia markers

Answer 23

CD11c, CD25, CD103

TRAP+

Question 24

Reed-Sternberg cell markers (classic HL)

Answer 24

CD15 and CD30

not: CD45, B-cell, T-cell antigens

Question 25

L and H or “popcorn” cell markers (nodular lymphocyte predominant HL)

Answer 25

CD45 and B-cell, including surface Igs

not: CD15 and CD30

Question 26

Langerhans cell markers

Answer 26

S100 and CD1a (immuno)
Birbeck granules (EM)