BL Flashcards
What is acute leukemia?
- Acute leukemia is a clonal, neoplastic proliferation of immature myeloid or lymphoid cells (two types as a result: AML and ALL) - Acute means it is rapidly fatal without treatment
How does acute leukemia work?
Immature leukemic cells that do not mature past a blast or other precursor stage accumulate in bone marrow and cause bone marrow dysfunction and there for loss of peripheral blood cells
What is the etiology of AML?
Chromosomal abnormalities affecting oncogenes, TS, or regulation of apoptosis lead to inability for cells to mature/differentiate and for them not to be regulated by external factors for growth and also inexhaustibly self-renews For AML, genetic disturbance at myeloid precursor –> AML types affecting myeloid lineages (granulocytes, monocytes, eythrocytes, megakaryocytes)
What is the etiology of ALL?
Similar to AML, but defect in lymphoid stem cell –> either B cell or T cell affected, but these cells don’t fully mature 75% of ALL cases occur in kids
What are risk factors for acute leukemia?
Chemotherapy (especially DNA alkylating agents and topoisomerase II inhibitors), smoking, ionizing radiation, benzene, other genetic syndromes (Down, Bloom, Fanconi anemia, ataxia-telangiectasia)
What are the signs and symptoms of acute leukemia?
Same things related to cytopenia: anemia (fatigue, dyspnea), thrombocytopenia (bruising, hemorrhage) neutropenia (fever/infection) However, sometimes present due to leukemic cells: thrombosis due to inc. WBC –> inc. blood viscosity, DIC initiated by WBCs, and can infiltrate mucouse membranes
What expresses CD34?
Immature lymphoblasts and myeloblasts
What expresses TdT?
Only lymphoblasts (no myeloblasts and no lymphocytes)
What do B-lymphoblasts express?
CD19, CD22, and/or CD79a, but not CD20 or surface Ig
Describe the cytogenetics of BALL
1) t(9:22)(q34;q11.2); BCR-ABL1 [Philadelphia chromosome] - 25% of adult cases (2% of child) - worst prognosis 2) 11q23; MLL - neonates/young infants - poor prognosis 3) t(12:21)(p13;q22); ETV6-RUNX1 - 23% of childhood BALL - very favorable prognosis
Describe T-ALL
Only 25-30% of ALL cases In adolescents/young adults primarily Presents more commonly with LBL with masses More likely to present with high WBC Males>females
What do T-lymphoblasts express?
CD2, CD3, and/or CD7; also CD4, CD8; also CD99, CD1a
What are other prognostic factors for ALL aside from cytogenetic findings?
Worse prognosis for 10yo/adults Worse if WBC is elevated Worse if hypodiploidy Worse if T-ALL
What is the diagnostic criteria for AML?
Either myeloblasts accounting for >20% of nucleated cells in the marrow/peripheral blood (detected through smears, flow cytometry, or immunohistochemistry on marrow biopsy) OR one of the genetic mutations
What do immature myeloblasts express?
CD34 (but also on lymphoblasts), CD117, myeloperoxidase, For monocytic diff –> CD64, CD14 For megakaryoblastic diff –> CD41, CD61 Also contain Auer rods (which help to distinguish from lymphoblasts)
Describe the cytogenetics of AML
Typically balanced translocations 1) t(8;21)(q22;q22); RUNX1-RUNX1T1 - 5% of cases - AML w/ maturation (some neutrophil production) - blocked transcription of CBF-dep genes –> blocked differentiation - good prognosis 2) inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11 - 5-10% of cases - lots of immature eosinophils with abnormal basophilic granules (baso eos) - inc. myeloblasts and monocytes (myelomonocytic leukemia) - similar to CBF in (1) - good prognosis *3) t(15;17)(q22;q12);PML-RARA - **important** - promyelocytes instead of blasts - 5-10% of cases - hypergranular (normal promyelocytes with lots of granules, Auer rods) - retinoic acid receptor alpha (RARA) needed for promyelocytes to deveop, but can overcome by giving retinoic acid - can cause DIC 4) t(1;22)(p13;q13);RBM15-MKL1 - megakaryoblastic diff - seen in infants w/ Down syndrome - good prognosis w/ chemo 5) 11q23; MLL - monocytic diff - poor prognosis
Describe the differences between therapy related AML secondary to alkylating agents/radiation and topoisomerase II inhibitors
AA/radiation - 2-8yrs of latency - goes through MDS before AML - whole or partial loss from chromosome 5 and/or 7 topoisomerase II inh - 1-2 years of latency - de novo AML skipping MDS - rearrangement of MLL gene (11q23) both have poor prognoses
What if there are no cytogenetic findings?
Then called AML, NOS (not otherwise specified) and you look at differentiation of leukemic cells: - myeloid if myeloblasts - myelomonocytic if myeloblasts and monoblasts/monocytes - monoblastic/monocytic if monoblasts and monocytes (may infiltrate skin) - eyrthroid if myeloblasts but erythroid precursors are inc - megakaryblastic - if megakaryoblasts/cytes and have marrow fibrosis However, are finding some genetic abnormalities: - FLT3 ITD: poor prognosis - NPM1 - good prognosis - CEBPA - good prognosis
What about overall prognosis?
If poor prognosis, then 10years 60% of AML will go into remission after chemo Stem cell transplant is preferred treatment
What two factors characterize MDS?
Ineffective hematopoiesis and increased risk of transformation to AML (basically similar to AML)
How do you diagnose MDS?
Look for 2+ cytopenias: anemia, thrombocytopeia, or neutropenia Look at marrow - >10% of cells should show dysplastic changes - dyserythropoiesis - RBC precurosors with moth-eaten and/or multi-lobed nuclei, sideroblastic - dysgranulopoiesis - moth eaten bi-lobed (Pelger-Huet) nuclei, abnormally pale (instead of pink) cytoplasm due to lack of granules - dysmegakaryopoiesis - small and single lobed nuclei Look at cytogenetics - partial or whole deletions of chr 5 and/or 7, deletion 7q, deletion 5q, trisomy 8
If no cytogenetics or increased myeloblasts and only dysplasia, then what?
Then need to exclude findings due to: - chemo - B12/folate def - viral infection - toxins
What is low and high grade MDS?
Low grade: 5% and/or >2%
What are the types of low grade MDS?
Refractory cytopenia with unilineage dysplasia - good prognosis - low grade MDS with dysplasia in only one lineage (usually anemia) Refractory cytopenia multilineage dysplasia - worse prognosis - 2+ lineages MDS w/ isolated deletion 5q - anemia, inc platelets, megakar with small, round, non lobed nuclei
