Hematopoietic Malignancies Flashcards
B-Cell Acute Lymphoblastic Leukemia/Lymphoma (B-ALL)
cell type involved
genetic/chromosomal aberrations
histologic identifiers
disease specific terms
patient presentation and complications
diagnostic techniques
pharmaceuticals
cytokines involved
most common cancer of children (85% of ALLs)
lymphoblasts (condensed chromatin, absent nucleoli, scant agranular cytoplasm)
loss-of-fxn mutations in trnx factors for B cells, some BCR-ABL1 translocations
many lymphoblasts in peripheral blood smear
leukocytosis, anemia (easy fatigue), thrombocytopenia, hepatomegaly, petechiae
immunophenotyping - TdT staining - for B cell markers (CD10, CD19, CD20, CD22) or T cell markers (CD1, CD2, CD5, CD7)
Acute Promyelocytic Leukemia (APL)
(type of Acute Myeloid Leukemia (AML))
cell type involved
genetic/chromosomal aberrations
histologic identifiers
disease specific terms
patient presentation and complications
diagnostic techniques
pharmaceuticals
cytokines involved
accumulation of myeloblasts (2/4 nucleoli, voluminous cytoplasm w/ granules) in bone marrow
t(15:17), PML-RAR-alpha fusion gene inhibits differentiation beyond promyelocyte
**Auer rods **(clumps/fibrils of azurophilic granules); seen in some types of AML, prominent in APL
anemia (easy fatigue), thrombocytopenia, neutropenia
**RT-PCR **(reverse transcriptase-PCR) - detects PML-RAR-alpha RNA; takes 2 days
ATRA (all-trans-retinoic acid) - reverses epigenetic silencing by inducing co-activators that recruit histone acetyltransferase; combined w/ cytotoxic chemotherapy, remission 80-95%
Hodgkin’s Lymphoma
cell type involved
genetic/chromosomal aberrations
histologic identifiers
disease specific terms
patient presentation and complications
diagnostic techniques
pharmaceuticals
cytokines involved
arises in a single node or chain of nodes, spreads nodal -> splenic -> hepatic -> marrow
Reed-Sternberg cells (germinal center B cells, multinucleate, inclusion-like nucleoli)
upregulation of NF-kappaB expression
lymph node fibrosis
painless, enlarged, firm, non-tender lymph nodes, sx of persistent infxn/allergy
lymph node bx
no tx listed
IL-5 (eosinophil activation), IL-10 (inhibition of TH1 and CTL), IL-13 (activates TH2)
T-Cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL)
cell type involved
genetic/chromosomal aberrations
histologic identifiers
disease specific terms
patient presentation and complications
diagnostic techniques
pharmaceuticals
cytokines involved
most common cancer of children (15% of ALLs)
more common in adolescent males
lymphoblasts (condensed chromatin, absent nucleoli, scant agranular cytoplasm)
NOTCH1 gain-of-fxn mutation
many lymphoblasts in peripheral blood smear
leukocytosis, anemia (easy fatigue), **thrombocytopenia, hepatomegaly, petechiae, sternal tenderness **(thymic lymphoma)
immunophenotyping - TdT staining - for T cell markers (CD1, CD2, CD5, CD7)
Chronic Lymphocytic Leukemia (CLL)
cell type involved
genetic/chromosomal aberrations
histologic identifiers
disease specific terms
patient presentation and complications
diagnostic techniques
pharmaceuticals
cytokines involved
most common leukemia of adults
mutated B cell Ag receptors cause Ag-independent autonomous pro-survival signaling
small lymphocytes, “smudge cells”
B cells w/ CD19/20/23 and T-cell associated CD5
**small lymphocytes, “smudge cells” in peripheral blood smear; lymphocyte infiltrates in bone marrow, splenic, and hepatic bxs and lymph nodes **(loss of nodal architecture)
leukocytosis, anemia, enlarged lymph nodes, feels fine
flow cytometry - to identify CD markers on B cells
ibrutinib - inhibits Bruton’s tyrosine kinase (responsible for cascade that leads to NF-kappaB activation)
NF-kappaB upregulated
Multiple Myeloma
cell type involved
genetic/chromosomal aberrations
histologic identifiers
disease specific terms
patient presentation and complications
diagnostic techniques
pharmaceuticals
cytokines involved
plasma cells w/ speckly nuclei, abundant cytoplasm w/ IgG staining, binucleate cells
**plasma cells in bone marrow, Bence-Jones proteins **(free IgG light chains in urine)
anemia (fatigue), thrombocytopenia, back pain, polyuria, polydipsia, proteinuria, bone lytic lesions, hypercalcemia, renal dysfxn
**bone marrow aspirate/bx; electrophoresis **- sharp monoclonal IgG band and IgGkappa monoclonal Ab
no listed tx
**increased IL-3 and IL-7 **inhibit osteoblast activity
Chronic Myelogenous Leukemia (CML)
cell type involved
genetic/chromosomal aberrations
histologic identifiers
disease specific terms
patient presentation and complications
diagnostic techniques
pharmaceuticals
cytokines involved
granulocytes (mature and maturing)
t(9:22), BCR-ABL1 fusion gene (Philadelphia chromosome)
peripheral blood smear/bone marrow aspirate show many granulocytes
leukocytosis, thrombocytosis, anemia, splenomegaly
fluorescence in-situ hybridization (FISH) - labeled DNA probes span breakpoint regions; in t(9:22) cell, labels overlap to produce distinct color; takes 24 hours
imatinib (Gleevec) - tyrosine kinase inhibitor, blocks ATP-binding domain
