Hematologic Malignancies 1

Question 1

When should you suspect hematologic malignancy?

Answer 1

1. Bone marrow is not functioning normally and can’t find an explanation –> low cell counts, high cell counts, or bone marrow cells in the blood
2. Lymphatic tissues have enlarged and infectious etiology can’t be found

Question 2

What is a blast?

Answer 2

Leukocyte that has 3 or 4 of these features:

1. Large cell
2. High nuclear to cytoplasmic ratio
3. Prominent, single or multiple nucleoli
4. Immature (faint) chromatin
5. Appearance is shared by many cells on a slide

Question 3

What are Auer rods?

Answer 3

Needle like eosinophilic crystals formed by proteins normally found in secondary granules –> typically myeloperoxidase
–> Always diagnostic of myeloid blasts

Question 4

What happens to bone marrow cellularity as you age?

Answer 4

Cellularity decreases –> Approximation is 100- age = % cellularity

Question 5

Limitations of flow cytometry in cell counting

Answer 5

1. RBC lysis procedure destroys erythroid precursors as well
2. Unusually large cells won’t be counted correctly
3. Cells can’t be immediately correlated with detailed morphological features

Question 6

Ways flow cytometry counts cells

Answer 6

1. Forward scatter detects cell size

2. Side scatter is high for cells with granules or segmented nuclei

Question 7

Flow cytometry and immunophenotyping

Answer 7

Fluorescent antibodies against CD45 (all bone marrow cells), CD34 (hematopoietic stem cells), or CD33 (granulocytes) plotted against side scatter to cluster cell types

Question 8

Philadelphia chromosome

Answer 8

9;22 translocation –> routine cytogenetic finding in chronic myelogenous leukemia

Question 9

Key advantage of FISH genotyping

Answer 9

Cells do not have to be growing to detect chromosomal abnormalities

Question 10

3 types of hematologic malignancies

Answer 10

1. Acute leukemia –> rapidly proliferating clones
2. Myeloproliferative disease –> Chronically proliferating and differentiating clones
3. Myelodysplastic syndrome –> poorly functioning clones

Question 11

Cells involved in to acute myeloid leukemia

Answer 11

1. Myeloid lineage
2. Erythroid lineage
3. Megakaryocytes

Question 12

Cells involved in acute undifferentiated leukemia

Answer 12

Hematopoietic stem cells

Question 13

Mutations in AML that blocks differentiation

Answer 13

PML-RARA (transcription factor), Tet1, Tet2 (inactivation of methylation), IDH1 and 2 (

Question 14

Mutations in AML that enhance proliferation

Answer 14

DNMT3A (DNA methylation enzyme), FLT3, KIT –> mostly tyrosine kinases with constitutive activity

Question 15

Mutation causing genetic instability in AML

Answer 15

TP53 mutation in both alleles –> leads to translocations, deletions, and fragmentation