Acute Leukemias

Question 1

List risk factors for acute leukemia

Answer 1

Previous chemotherapy (DNA alkylating Agents and Topoisomerase inhibitors)

Ionizing radiation

Tobacco Smoke

Benzene Exposure

Genetic syndromes; downs, bloom, fanconi anemia, ataxia telangiectasia

Question 2

List common signs and symptoms exhibited by patients with acute leukemia at initial presentation, and explain the reasons for these findings.

Answer 2

Fatigue, malaise, pallor, dypsnea

Bruising, petechiae, hemorrhage

Fever, infections

Rare:
Thrombotic events due to blood viscosity
DIC, initiated by leukemic cells in AML
Direct infiltration of skin/gums/nodes/other tissue

Question 3

ALL- Acute Lymphoblastic Leukemia

Answer 3

Neoplasm of precursor lymphoid

B-ALL or T-ALL

incidence of 1-5/100,000

75% of ALL occur in children less than 6 years old

Question 4

How to diagnose ALL

Answer 4

Blast is majority of marrow cells (Packed Marrow)

Peripheral blood WBC count increased/mild increase/normal/decreased

Question 5

Cell Markers for ALL

Answer 5

Immaturity markers- CD34
Lymphoblast marker- TdT (enzyme)
Markers of B Cell- CD19N CD22
Markers of T Cells- CD3, CD7

Question 6

B-ALL

Answer 6

80-85% of cases of ALL

B-lymphoblasts lack mature b cell markers

Typical ALL of childhood

Question 7

T(9;22) of B-ALL

Answer 7

t(9;22), deriavtive of Philadelphia Chromosome, 25% of adult ALL, but only 2% of children ALL

Different breakpoint than CML

Unfavorable prognosis

Question 8

11p23 MLL of B-ALL

Answer 8

Poor prognosis
MLL may be rearranged
Seen in neonates and young infants

Question 9

t(12;21) ETV6-RUNX1` of B-ALL

Answer 9

25% of child B-ALL

Favorable Prognosis

Question 10

T-ALL

Answer 10

Minority of ALL, 25%
More frequently in adolescents and young adults
Males over females
Elevated WBC count
Often presents with mediastinal mass

Question 11

ALL Treatment

Answer 11

Good prognosis disease for the most part in chidlren
Remission rates of >90%, cure rate ~80%

For adults, pronosis is worse

Question 12

Prognosis factors for ALL

Answer 12

Age (Kids do better, older gets worse)
# of WBC count
If it's T or B lymphoblast (T is worse)
Hyperdiploidy > Hypodiploidy
Speed of response to therapy (slow is bad)

Question 13

AML, Acute Myeloid Leukemia

Answer 13

More heterogenous than ALL, so more types

Adult disease mostly, average age is 65 for diagnosis

3/100,000 per year, similar to ALL

Question 14

Diagnosing AML

Answer 14

presence of >=20% myeloblasts in marrow or blood

Look for markers: CD34 (immaturity), CD117/Myeloperoxidase (myeloid markers)

Question 15

Auer Rods

Answer 15

Fused granules forming small stick like structures in cytoplasm. PResence = blast of myeloblast, and abnormal

Question 16

AML with t:8;21); RUNX1-RUNX1T1

Answer 16

5% 
Younger patients
AML with maturation
Mutation of a core binding factor needed for differentiation
Relatively good prognosis
Presence = diagnosis

Question 17

AML with inv(16) or t(16;16); CBFB-MYH11

Answer 17

5-10% of AML
Younger patients
Good prognosis
Presence = diagnosis
Smear has presence of Beso Eos

Question 18

APL with t(15;17), PML-RARA

Answer 18

5-10%
acute promyelotic leukemia, accuulation of promyelocytes
Hypergranular morphology
Multiple auer rods
Presence = diagnosis

Question 19

Why is t(15;17) PML RARA so important

Answer 19

1. RARA gene = retinoic acid receptor, required for differentiation

Fusion protein encodes for defective receptor, so poor signalling. Works are higher doses of ligand

Can treat patients with ATRA, which is high dose retinoic acid

2. APL is associated with DIC, so best to avoid that as early as possible

Question 20

AML with t(1;22) RMB15-MKL1

Answer 20

Megakaryoblastic differentiation
Common in infants with downs syndrom
Relatively good prognosis

Question 21

AML with 11q23; MLL gene

Answer 21

Poor prognosis, monocytic differentiation

Question 22

Therapy Related AML (T-AML)

Alkylating agent

Answer 22

2-5year latency, complex karyotype, usually progress to AML through MDS

Poor prognosis

Question 23

Therapy Related AML (T-AML)

Topoisomerase Inhibition

Answer 23

1-2 year latency, just reaarangement of 11q23, does not progress to AML

Poor prognosis

Question 24

Molecular Markets to predict prognosis

Answer 24

FLT 3, most important, poor prognosis, trumps the other two

Nucleophosphin1 (NPM1), good prognosis

CEBPA, good prognosis

Question 25

Leukemic Stem Cell

Answer 25

Cell with potential for self renewel for all different types of myeloid cells (granulocytic, monocytic, erythroid, megakaryocytic).

An inexhaustable supply