Acute Leukemias (complete)

Question 1

Describe leukemic stem cells

Answer 1

• Potential for crazy amounts of self renewal
• Also differentiate into leukemic blasts cells
• THIS IS WHERE IT ALL BEGINS!

Question 2

What are the risk factors for acute leukemia? — Remember, however, that majority of acute leukemias occur in absence of risk factors

Answer 2

1) Previous chemo (remember DNA damage from alkylating agents or topoisomerase II inhibitors)
2) Tobacco smoke
3) Ionizing radiation
4) Benzene exposure
5) Genetic syndromes (e.g. Down syndrome, Bloom syndrome, Fanconi anemia, ataxia-telangiectasia)

Question 3

What are the common signs/symptoms exhibited by pts w/ acute leukemia at initial presentation?

Answer 3

Symptoms of anemia

1) Fatigue
2) Malaise
3) Dyspnea
4) Pallor

Symptoms of thrombocytopenia

1) Easy bruising
2) petechiae
3) Hemorrhage

Symptoms of neutropenia

1) Fever
2) Infections

Question 4

Why are the signs and symptoms exhibited by pts w/ acute leukemia at initial presentation?

Answer 4

Decreased #s of normal peripheral blood cells — b/c of marrow infiltration by leukemic cells

Low platelets
Low RBCs
Low neutrophils

Question 5

What are a few basic markers that would help to assign blasts to a precursor-B, precursor-T, or myeloid lineage?

Answer 5

Pre-B: CD19, CD22

Pre-T: CD3, CD7

Mye: CD34 (myeloblasts)

Lymph: TdT (lymphoblasts)

Question 6

Constrast B-ALL and T-ALL in regards to pt age and sex, manner of manifestation, and prognosis

Answer 6

For T-ALL compared to B-ALL…

Age: adolescents, YA

Sex: favors males

M: presents w/ a component of T-LBL, or mediastinal mass (B-ALL no lymphoma, only leukemia)
- Have markedly elevated WBC count

Question 7

What are 3 commonly observed cytogenetic abnormalities in B-ALL?

Answer 7

1) t(9;22)(q34;q11.2) — BCR-ABL1
2) t(11q23) — MLL
3) t(12;21)(p13;q22) — ETV6-RUNX1

Question 8

What is the usual pt age group and prognosis associated with BCR-ABL1?

Answer 8

Philadelphia chromosome (Ph+ ALL)

A: adults, children

P: worst prognosis of any subtype of ALL

Question 9

What is the usual pt age group and prognosis associated with MLL (ALL)?

Answer 9

A: neonates, young infants

P: poor

Question 10

What is the usual pt age group and prognosis associated with ETV6-RUNX1?

Answer 10

A: children

P: very favorable!

25% of cases in childhood B-ALL

Question 11

What are the 5 factors affecting prognosis in ALL? Worse prognosis in parentheses.

Answer 11

1) Age (less than 1yo, more than 10yo, adults)
2) WBC count (elevated @ diagnosis)
3) Slow response to therapy or small amounts of disease after therapy
4) # of chromosomes (<46 chromosomes)
5) B vs. T lineage (T has it bad)

Question 12

What are 2 types of findings that would allow for diagnosis of AML?

Answer 12

Increased myeloblasts accounting to >20% of nucleated cells in…

1) BM or
2) peripheral blood

Question 13

What is an Auer rod? What is its clinical significance?

Answer 13

• Fused azurophilic granules forming small stick-like structures in cytoplasm
• Only seen in abnormal myeloblasts
• Can be used in diagnosis of AML!

W/o Auer rods, you can’t differentiate btwn myeloblasts and lymphoblasts in a smear

Question 14

What are the 5 recurrent cytogenetic abnormalities for AML?

Answer 14

1) t(8;21) — RUNX1-RUNX1T1
2) inv(16) or t(16;16) — CBFC-MYH11
3) t(15;17) — PML-RARA
4) t(1;22) — RBM15-MKL1
5) 11q23 —MLL

Question 15

What is the usual pt age group and prognosis associated with RUNX1-RUNX1T1 — t(8;21)?

Answer 15

A: younger pts (20s, 30s, 40s)

P: Good prognosis

Question 16

What is the usual pt age group and prognosis associated with CBFC-MYH11 — inv(16) or t(16;16)?

Answer 16

A: younger pts (20s, 30s, 40s)

P: Good prognosis

Associated w/ presence of abnormal eosinophilic percursors w/ abnormal basophilic granules and eos granules (BASOS EOS!!)

Question 17

What is the usual pt age group and prognosis associated with RBM15-MKL1 — t(1;22)?

Answer 17

A: infants w/ Down syndrome

P: Good prognosis

Shows megakaryoblastic differentiation

Question 18

What is the usual pt age group and prognosis associated with MLL (AML) — 11q23?

Answer 18

A: kids and adults

P: Poor prognosis

Question 19

Explain 2 reasons why it is important to recognize at initial diagnosis that a case of AML is the AML w/ t(15;17) subtype of AML (aka: acute promyelocytic leukemia, APL)

Answer 19

1) Encodes alpha-subunit of retinoic acid — signaling required for a receptor to begin differentiation past the promyelocyte stage
- A mutation in this is a problem!
- Can be mitigated w/ retinoic acid therapy

2) Associated w/ DIC (crazy clotting and hemorrhage)

Question 20

Contrast the 2 main categories of therapy-related AML. Talk about latency, cytogenetic abnormalities, and processes to AML through an MDS stage

Answer 20

1) Alkylating agents/radiation
2) Topoisomerase Inhibitors

AA/R vs TI

L: 2-8 y vs. 1-2 y

C: complex karyotype w/ whole/partial deletions in 5 or 7 vs. rearrangement of 11q23 (MLL)

MDS?: Usually yes vs. usually no

Question 21

Compare the prognosis of the 2 main categories of therapy-related AML

Answer 21

Both BADDDDDD

Question 22

What are the 3 molecular markers currently used to predict prognosis in pts w/ AML w/ normal karyotype?

Answer 22

1) FLT3 ITD
2) NPM1
3) CEBPA

Question 23

Of the 3 molecular markers currently used to predict prognosis in pts w/ AML w/ normal karyotype, which of these trumps the other 2 as a driving prognostic factor?

Answer 23

FLT3 ITD!

You only check for NPM-1 or CERPA if you are negative for FLT3

Question 24

What are the surface markers used to diagnose AML?

Answer 24

1) CD34 (lymphoblasts)
2) CD117 - C-Kit (myeloid marker)
3) Myeloperoxidase (myeloid marker)