AML

Question 1

t(8:21)

Answer 1

Runx1-Runx1T1

Question 2

t(8:21)

Answer 2

• -fusion protein of two transcription factors
• -5% of AML cases
• -Class II mutant (dominant repressor of myeloid maturation)

Question 3

t(8:21)…Clinical presentation

Answer 3

younger pts/ kids

Question 4

t(8:21)…Morphology

Answer 4

• -Some maturation to myelocytes

- -Occasional crystallization of granule contents (“Auer rods”)

Question 5

t(8:21)…Immunophenotyping

Answer 5

CD34+
HLA-DR+
CD13+
CD33 weak

Question 6

t(8:21)…Prognosis

Answer 6

Good Response to chemo

Question 7

t(15;17)(q22;q12)

Answer 7

PML-RARA

Question 8

t(15;17)

Answer 8

• -Fusion of PML (transcription factor) with RARA (transcription factor - retinoic acid receptor)
• -5-8% of AML cases

Question 9

t(15;17)

Answer 9

Previously called AML-M3 or acute promyelocytic leukemia!!! (APL)

Question 10

t(15;17)

Answer 10

• -Dominant negative blockade of normal RARA
• -Inhibits Granulocyte differentiation (Class II mutation)
• -(requires concomitant Class I mutation)

Question 11

t(15;17)… Treatment (see Pharm form more on treating APL)

Answer 11

• -PML-RARA itself can be blocked with an RA analogue (ALL TRANS RETINOIC ACID, or ATRA)
• -ATRA induces differentiation of the blasts to granulocytes CLINICAL REMISSION
• **OTHER TRANSLOCATIONS TO RARA FROM OTHER LOCATIONS THAT PRODUCE APL MAY NOT RESPOND TO ATRA!!!!

Question 12

t(15;17)…Clinical Presentation

Answer 12

• -DIC

- -Severe thrombocytopenia

Question 13

t(15;17)…Morphology

Answer 13

• -Big blasts
• -Cleaved, “bat wing” nuclei
• -Many cytoplasmic granules
• -Aurer rods in stacks

Question 14

t(15;17)…Immunophenotype

Answer 14

Weak/absent CD34
HLA-DR
CD13+
CD33+

Question 15

t(15;17)…Prognosis

Answer 15

Good if diagnosis is made

Question 16

CBFB-MYH11

Answer 16

inv(16)
OR
t(16:16)

Question 17

CBFB-MYH11

Answer 17

• -Fusion protein of transcription factors w/ MYH1
• -5-8% of AML cases
• -Class II Mutant (dominant negative repressor of myeloid maturation)
• -Probably requires concurrent Class I mutation

Question 18

CBFB-MYH11…Clinical presentation

Answer 18

younger pts/ kids

Question 19

CBFB-MYH11…Morphology

Answer 19

• -Mixed granulocyte-monocyte features (“Myelomonocytic”)

- -Increased eosinophils in blood and marrow

Question 20

CBFB-MYH11…Immunophenotype

Answer 20

CD34+
CD117+ (blasts)
CD13+
CD33+ (granulocytes)
CD14+
CD11b+ (monocytes)

Question 21

CBFB-MYH11…Prognosis

Answer 21

Variably poor; optimal w/ high dose cytarabine
(SEE PHARM NOTES)
inv(16) prognosis good

Question 22

AML w/ normal cytogenetics

Answer 22

40-50% of AML cases

Question 23

AML w/ normal cytogenetics…Clinical Presentation

Answer 23

any age group

Question 24

AML w/ normal cytogenetics…Morphology

Answer 24

undifferentiated OR
variably granulocytic OR
monocytic/monoblastic

Question 25

AML w/ normal cytogenetics...Immunophenotype

Answer 25

``` Blast markers (CD34, CD117)+ can show any lineage markers ```

Question 26

AML w/ normal cytogenetics...Prognosis

Answer 26

Depends on molecular genetics

Question 27

AML w/ normal cytogenetics | NPMN1 or CEBPA+, FLT3-ITD-

Answer 27

60% 4 yr. survival | bone marrow transplant doesn't help

Question 28

AML w/ normal cytogenetics | FLT3-ITD+ or NPM1-, CEBPA-, FLT3-ITD-

Answer 28

29% 4-yr survival | Bone marrow transplant helps

Question 29

Poor prognosis AML

Answer 29

Complex (>3 clonal chromosomal abnormalities) Partial monosomy (i.e. del(5q)) 11q23 t(9:22)