Introduction to Leukemia (Exam III) Flashcards
Definition of leukemia
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
Etiology
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
First) BM becomes crowded
Neoplastic cells proliferate
(need to identify)
Second) Normal hematopoiesis hindered
Anemia and Thrombocytopenia
Third) Extramedullary hematopoiesis
Hepatosplenomegaly
Myeloid lineage
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
Lymphoid lineage
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
Acute Leukemia
Rapidly progressive disease characterized by an abnormal expansion of immature cells or blasts
Chronic leukemia
Slowly progressive disorder characterized by an abnormal expansion of mature cells
Acute Leukemia
Age
Clinical Onset
Course (untreated)
Leukemic Cells
Anemia
Thrombocytopenia
Organomegaly
- All ages
- Sudden
- Months
- Immature
- Mild-Severe
- Mild-Severe
- Mild
Chronic Leukemia
Age
Clinical Onset
Course (untreated)
Leukemic Cells
Anemia
Thrombocytopenia
Organomegaly
- Adults
- Insidious
- Years
- Mature
- Mild
- Mild
- Prominent
Leukemia Broad Groups
- Acute Myeloid Leukemia
- Acute Lymphoblastic Leukemia
- Chronic Myeloid Leukemia
- Chronic Lymphocytic Leukemia
Cytogenetics
detects # and structural variations in chromosomes
karyotyping
stained metaphase chromsomes
FISH
Fluorescent in Situ Hybdridization - detects smaller genetic abnormalities
Molecular Genetics
Detcts changes at the DNA level in a single gene
Genetics nomenclature
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
Q arm
long arm
P arm
Short arm
BCR-ABL
gene product from abnormality
Cell surface markers
Proteins on the cell membrane
Cytoplasmic markers
proteins in the cytoplasm
Cell surface markers and cytoplasmic markers
can be detected using flow cytometry or immunohistochemistry
cytoplasmic markers
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
Flow cytometry
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
Immunohistochemistry
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
Age ALL
more common in children
Age AML
more common in adults
Age CLL and CML
more common in adults
Onset
Abrupt, more common in acute leukemia
ALL and AML
Onset
Gradual, more common in chronic leukemia
CML and CLL
Auer Rods
- Needle like bodies in Myeloblast or Promyelocyte
- Cause = fusion of primary granules
- Acute Myelogenous leukemia (AML)
- Acut Monocytic Leukemia
Leukemoid reaction
High LAP score
Chronic myelogenous leukemia (CML)
Low LAP score
LAP positive staining
Blue intensified granules
LAP stains neutrophilic granules
present in segmented neutrophils, bands, metamyelocytes
Cytogenetics
number and structural variations in chromosomes
molecular genetics
identify translocations, inversions, mutations
immunophenotype
cell marker expression (flow cytometry or immunohistochemistry)
Clinical features
Symptoms, onset etc.
Microscopic morphology
identifiable cellular details
Cytochemistry
Special stains to identify enzymes or lipids specific to certain blast populations
French-American-British (FAB)
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
WHO system
Requires >20% myeloblasts in blood or BM = Acute Myeloid Leukemia
Requires >25% lymphoblasts in BM = Acute Lymphoblastic/cytic Leukemia
ALL/Lymohoma ->
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
WHO genetics
AML withh recurent genetic abnormalities
WHO secondary/history
- AML with myelodysplasia related changes
- Therapy related myeloid neoplasms
- Myeloid proliferations realted to downs syndrome
WHO morphology/cytochemistry/Immunophenotype
- AML not otherwise specified (NOS)
- Blastic Plasmacytoid dendritic cell neoplasm
WHO Immunophenotype Undifferentiated or mixed
Acute leukemias of ambigious lineage
WHO myeloid neoplasms outside of BM
Myeloid sarcoma
WHO Myeloid neoplasm in background
Myeloid neoplasms with germline predisposition
