Introduction to Leukemia (Exam III)

Question 1

Definition of leukemia

Answer 1

malignant disease of hematopoietic tissue that is characterized by replacement of normal BM elements with abnormal (neoplastic) blood cells

• leukemic cells are frequently (NOT always) present in the peripheral blood
• Commonly invade reticuloendothelial tissue (spleen, liver, and lymph nodes) and can invade other organs

Question 2

Etiology

Answer 2

Mutation or altered expression of oncogenes or tumor suppressor genes
- regulate cell proliferation and differentiation

Abnormal oncogene or tumor suppressor gene expression -> unregulated cellular proliferation

Question 3

First) BM becomes crowded

Answer 3

Neoplastic cells proliferate

(need to identify)

Question 4

Second) Normal hematopoiesis hindered

Answer 4

Anemia and Thrombocytopenia

Question 5

Third) Extramedullary hematopoiesis

Answer 5

Hepatosplenomegaly

Question 6

Myeloid lineage

Answer 6

Related to cell lineages from Myeloid Stem Cell
- includes cell lines that divide and mature iN BM
- Granulocytic (neutrophils, basophils, eosinophils), Erythrocytic (RBCs), megakaryocytic (platelets), monocytic (monocytes/macrophages) and all of their precursors

Question 7

Lymphoid lineage

Answer 7

Relating to cell lineages from lymphoid stem cell
- includes cell lines that mature in the lymphatic system (spleen, thymus, lymph nodes)
- B&T lymphocytes and their precursors

Question 8

Acute Leukemia

Answer 8

Rapidly progressive disease characterized by an abnormal expansion of immature cells or blasts

Question 9

Chronic leukemia

Answer 9

Slowly progressive disorder characterized by an abnormal expansion of mature cells

Question 10

Acute Leukemia
Age
Clinical Onset
Course (untreated)
Leukemic Cells
Anemia
Thrombocytopenia
Organomegaly

Answer 10

• All ages
• Sudden
• Months
• Immature
• Mild-Severe
• Mild-Severe
• Mild

Question 11

Chronic Leukemia
Age
Clinical Onset
Course (untreated)
Leukemic Cells
Anemia
Thrombocytopenia
Organomegaly

Answer 11

• Adults
• Insidious
• Years
• Mature
• Mild
• Mild
• Prominent

Question 12

Leukemia Broad Groups

Answer 12

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Chronic Myeloid Leukemia
• Chronic Lymphocytic Leukemia

Question 13

Cytogenetics

Answer 13

detects # and structural variations in chromosomes

Question 14

karyotyping

Answer 14

stained metaphase chromsomes

Question 15

FISH

Answer 15

Fluorescent in Situ Hybdridization - detects smaller genetic abnormalities

Question 16

Molecular Genetics

Answer 16

Detcts changes at the DNA level in a single gene

Question 17

Genetics nomenclature

Answer 17

Ex: Philadelphia chromosome - CML
- t(9;22)(q34;q11)(BCR-ABL)
- t = trnaslocation (transfer of one portion of a chromosome to another)
- inversion = breaks off and reattaches upside down
- () surrounds structurally altered chromosomes and breakpoints

Question 18

Q arm

Answer 18

long arm

Question 19

P arm

Answer 19

Short arm

Question 20

BCR-ABL

Answer 20

gene product from abnormality

Question 21

Cell surface markers

Answer 21

Proteins on the cell membrane

Question 22

Cytoplasmic markers

Answer 22

proteins in the cytoplasm

Question 23

Cell surface markers and cytoplasmic markers

Answer 23

can be detected using flow cytometry or immunohistochemistry

Question 24

cytoplasmic markers

Answer 24

Quantity of antigen on the cell surface and in cytoplasm varies

Some antigens are exclusively cytoplasmic

When using flow cytometry for detection, we have to add a step
- Permeabilize cells - allows antibody being used for detection to enter the cytoplasm

Question 25

Flow cytometry

Answer 25

Requires a cell suspension - Typically bone marrow aspirate or peripheral blood Want fresh speciment with viable cells Uses immunoflorescence to stain the cells - Fluorochrome (antibody conjugated to fluorescent dye) binds to a specific antigen Cells then flow in a single file line through detector - detects fluorescence of fluorochrome - Can also measure size (FSC) and granularity (SSC) of cell from light scatter

Question 26

Immunohistochemistry

Answer 26

Performed on paraffin sections of the core biopsy, BM clot, or other biposy material - specimen must be fized Antibodies conjugated to an enzyme (or fluorescent dye) bind to specific antigens - a substrate is added that is catalyzed by the bount enzymes producing a color reaction

Question 27

Age ALL

Answer 27

more common in children

Question 28

Age AML

Answer 28

more common in adults

Question 29

Age CLL and CML

Answer 29

more common in adults

Question 30

Onset Abrupt, more common in acute leukemia

Answer 30

ALL and AML

Question 31

Onset Gradual, more common in chronic leukemia

Answer 31

CML and CLL

Question 32

Auer Rods

Answer 32

- Needle like bodies in Myeloblast or Promyelocyte - Cause = fusion of primary granules - **Acute Myelogenous leukemia (AML)** - Acut Monocytic Leukemia

Question 33

Leukemoid reaction

Answer 33

High LAP score

Question 34

Chronic myelogenous leukemia (CML)

Answer 34

Low LAP score

Question 35

LAP positive staining

Answer 35

Blue intensified granules

Question 36

LAP stains neutrophilic granules

Answer 36

present in segmented neutrophils, bands, metamyelocytes

Question 37

Cytogenetics

Answer 37

number and structural variations in chromosomes

Question 38

molecular genetics

Answer 38

identify translocations, inversions, mutations

Question 39

immunophenotype

Answer 39

cell marker expression (flow cytometry or immunohistochemistry)

Question 40

Clinical features

Answer 40

Symptoms, onset etc.

Question 41

Microscopic morphology

Answer 41

identifiable cellular details

Question 42

Cytochemistry

Answer 42

Special stains to identify enzymes or lipids specific to certain blast populations

Question 43

French-American-British (FAB)

Answer 43

Microscipic morphology - identifiable cellular details Cytochemistry - special stains to identify enzymes or lipids specific to certain blast populations **Requires >30% blasts in blood or MB = Acute leukemia**

Question 44

WHO system

Answer 44

**Requires >20% myeloblasts in blood or BM = Acute Myeloid Leukemi**a **Requires >25% lymphoblasts in BM = Acute Lymphoblastic/cytic Leukemia**

Question 45

ALL/Lymohoma ->

Answer 45

B cells - B cell lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities - B cell lymphoblastic leukemia/lymphoma, not otherwise specified T cells - Early T cell precursors lymphoblastic leukemia - Natural Killer (NK) cell lymphoblastic leukemia/lymphoma

Question 46

WHO genetics

Answer 46

AML withh recurent genetic abnormalities

Question 47

WHO secondary/history

Answer 47

- AML with myelodysplasia related changes - Therapy related myeloid neoplasms - Myeloid proliferations realted to downs syndrome

Question 48

WHO morphology/cytochemistry/Immunophenotype

Answer 48

- AML not otherwise specified (NOS) - Blastic Plasmacytoid dendritic cell neoplasm

Question 49

WHO Immunophenotype Undifferentiated or mixed

Answer 49

Acute leukemias of ambigious lineage

Question 50

WHO myeloid neoplasms outside of BM

Answer 50

Myeloid sarcoma

Question 51

WHO Myeloid neoplasm in background

Answer 51

Myeloid neoplasms with germline predisposition