Hematology - malignant

Question 1

What are some of the acquired chromosomal abnormalities in the transition from chronic phase CML to accelerated phase?

Answer 1

Trisomy 8

Chr7, particularly t7;11(p15;p15) = NUP98-HOXA9 fusion

Question 2

What are the good prognostic indicators in pre B-ALL?

Answer 2

Hyperdiploidy 51-65 (DI 1.16 – 1.6) t(12;21)(p12;q22) TEL-AML1,

Question 3

What are the bad prognostic indicators in pre B-ALL?

Answer 3

t(9;22) BCR-ABL

t(4;11) MLL-AF4

t(1;19) E2A-PBX Hypodiploidy

>5 x ETV6 hyperdiploidy = iAMP

Question 4

What mutatation is most commonly found in peds AML comparted with adult AML?

Answer 4

KMT2a (MLL)

Question 5

What germline mutations predispose to pediatric AML?

Answer 5

ETV6

RUNX1

CEBPA

GATA2

ANKRD26

Question 6

List the most common translocation associated AMLs in patients without germline abnormalities.

Answer 6

MLL (KMT2a) = 20%

CBF: inv16 (MYH11) = 10%

CBF: t8;21 (RUNX1) = 15%

NPM1 = 15%

WT1 = 10%

CEBPA = 5%

Question 7

What genetic abnormalities are seen in pediatric MDS with progression to AML?

Answer 7

Monosomy 7, 7q-

Monosomy 5, 5q-

20q-

Question 8

What genetic abbarency is the MCC of peds MDS?

Answer 8

Monosomy 7

Question 9

What is the most common cytogenetic abnormality in peds AML <2yo?

Answer 9

MLL translocations (11q23)

Question 10

What is the most common type of AML in Down’s Syndrome?

What is the associated mutation?

What is the translocation associated in these patients without Down’s?

Is there a prognostic difference between Down’s and non-Down’s patients?

Answer 10

Acute Megakaryoblastic Leukemia (AMKL)

GATA-1

t(1;22)(p13;q13)

Down’s = excellent; non-Down’s = very poor

Question 11

What is the frequency of AML in Down’s patients?

Answer 11

1/500

Question 12

What hereditary conditions increase the risk of developing MDS/AML?

Answer 12

Down

Noonan

Fanconi anemia

Bloom

Kostmann

Shwachman-Diamond

Klinefelter

NF1 (JMML)

Question 13

What acquired conditions increase the risk of developing MDS/AML?

Answer 13

Aplastic anemia, PNH, JMML

Question 14

What are the APL translocations?

Answer 14

t15;17 (PML-RARA)

t11;17 (PLZF-RARA)

t5;17 (NPM-RARA)

t11;17 (NuMA-RARA)

t11;17 (STAT5b-RARA)

*Bonus: FLT3 mutations occur in 43% of APLs, and more often microgranular with hyperleukocytosis and bcr3 PML breakpoint

Question 15

What translocation is present in adult DLBCL, but negative in pediatric DLBCL?

Answer 15

t(14:18) IGH/BCL2