Acute Leukemias

Question 1

Acute Lymphoblastic Leukemia demographics

Answer 1

75% in kids under 6

Question 2

lymphoblast histologic characteristics

Answer 2

large, high N/C ratio, visible nucleoli

Question 3

lymphoblast marker

Answer 3

TdT–DNA polymerase in lymphoblast nucleus

Question 4

ALL B-cell/T-cell lineage markers

Answer 4

CD19, CD22

CD3, CD7

Question 5

B-cell ALL characteristics

Answer 5

80% of ALL cases, typically childhood

Lymphs usually lack maturity markers such as CD20

Question 6

B-cell ALL translocations

Answer 6

t(9;22) BCR-ABL1–>Philadelphia ch., results in fusion tyrosine kinase. 190 kD protein, as opposed to 210 kD in CML, so can’t treat w/ Gleevec. Most common in adults. Poor prognosis.

11q23. MLL. In neonates and infants. Poor prognosis

t(12;21). Childhood, favorable prognosis

Question 7

T-cell ALL characteristics

Answer 7

Freq. in adolescence. Presents w/ mediastinal mass, elevated WBCs. Usually in males

Question 8

ALL prognostic factors

Answer 8

Younger=better, high WBC=worse, diploidy=worse

Question 9

Acute Myelogenous Leukemia general

Answer 9

avg age of diagnosis=65

Question 10

AML Diagnosis

Answer 10

greater than 20% myeloblasts in marrow/blood by morphology, flow, IHC

Question 11

Blast (myeloid & lymphoid) immaturity marker

Answer 11

CD34

Question 12

Myeloid markers

Answer 12

CD117 (c-kit), myeloperoxidase

Question 13

Myeloblast histology

Answer 13

high N/C ratio, in AML, AUER RODS (crystallized myeloperoxidase)

Question 14

AML translocations

Answer 14

t(8;21)–AML w/ maturation–some mature neuts, good prognosis. DIAGNOSTIC OF AML REGARDLESS OF BLAST COUNT
inv(16)/t(16;16)–abnormal eosinophilic precursors, leukemic cells are a mix of monocytes and myeloblasts. good prognosis
t(15;17) PML-RARA–known as acute promyelocytic leukemia APL. Cells blocked @ promyelocyte stage.
t(1;22)–megakaryoblastic proliferation. Characteristic in infants w/ DS. good prog
11q23–MLL–poor prog, as in ALL w/ MLL abnormality

Question 15

t(15;17)

Answer 15

PML-RARA. Acute promyelocytic leukemia. Cells blocked at promyelocyte stage. RARA encodes retinoic acid receptor alpha protein, which is required for differentiation. In APL, fusion protein functions poorly as a receptor, so cells don’t mature. administration of all trans retinoic acid (ATRA) can give adequate signaling.
Patients do not require chemo. Multiple Auer rods can activate coagulation pathway, so DIC is a concern

Question 16

t-AML

Answer 16

therapy related–alkylating agents, radiation. very bad prognosis. complex karyotype

Question 17

AML NOS

Answer 17

not otherwise specified. lack of cytogenetic findings. FLT3 internal tandem duplication–> poor prog