Intro to Leukemias

Neoplasm

Neoplasm

abnormal formation of new tissue that serves no useful purpose

leukemia

generalized abnormal neoplastic proliferation and diff arrest of immature hematopoietic cells which lead to accumulation in BM and peripheral

Oncogenes

mutated genes that lead to the transformation of a normal cell to a cancer

Proto-oncogne

normal counterpart of oncogene

tumor suppressor gene

hereditary unit whose protein products function to inhibit the growth of normal cells

what are the 2 major cytological classifications

lymphocytic (lymphoid progenitor) and non-lymphocytic (myeloid progenitor)

Acute leukemia

- precursor neoplasm
- refractory to remission
- fatal in 3 months
- > 20% blasts in BM

Chronic leukemia

- mature neoplasm
- longer prognosis
- < 10% blasts in BM
- wider variety of cells

What are some non-specific symptoms (seen in other diseases) for leukemia?

fatigue, low grade fever, N/V, anemia, infection, bleeding episodes (thrombocytopenia)

What are more specific symptoms for leukemia?

- enlargement of lymph nodes, liver, and spleen
- bone pain (sternum)
- chronic headache

What are common lab findings for leukemia?

anemia (n/n), leukocytosis, thrombocytopenia, basophilia, blasts in BM, NRBCs in peripheral blood

What are non-hematological clues for leukemia?

Inc in Uric acid, LDH, vitamin B12 and binding capacity, muramidase (greatly inc in monocytic leukemias)

What happens after the activation of a proto-oncogene?

stimulates proliferation and inhibits apoptosis

The inactivation of tumor suppressor genes leads to what?

loss of proliferation control, block of maturation and differentiation

Cytogenetic Analysis

- analyzing cells in a sample to look for changes in chromosomes (translocations most common)
- during metaphase
- help monitor therapy, survival, remission, relapse

Philadelphia Chromosome (Ph1)

- >90% CML
- t(9;22)
- makes BCR-ABL gene and protein

What does the BCR-ABL protein do?

provides kinase activity which stimulates CML cell proliferation

Immunophenotyping by Flow

- CD markers used to ID and investigate hematopoietic cells
- used to ID leukemic cells, predict prognosis, predict treatment response, monitor progression/relapse

What is the CD marker for Hematopoietic Stem cells?

CD34

All differentiated WBCs have which CD marker?

CD45