Flashcards in Acute Leukemias Deck (33):
CBC chart diagram
WBC, Hgb/Hct, Platelets
abrupt onset of pancytopenia (decrease in all cell types). dysfunctional immature neoplastic cells replace everything. quickly become sick
immature neoplastic cells predominate
mature neoplastic cells predominate
what types of leukemias are better prognostically?
acute better than chronic
myeloid better than lymphoid
myeloproliferative neoplasms (MPNs)
clonal expansion of an abnormal hematopoietic stem cell with retained differentiation leading to expansion of mature hematopoietic cells. can become ALL or AML
subtypes of myeloproliferative neoplasms
polythemia vera, essential thrombocytosis, chronic myeloid leukemia, chronic idiopathic myelofibrosis (RBCs, platelets, neutrophils, megakaryocytic respectively)
clonal expansion of an abnormal HSC with abnormal differentiation leading to decreased number of mature hematopoietic cells, resulting in anemia, thrombocytopenia, or neutropenia. can lead to AML (rarely ALL)
what types of chemotherapy can lead to acute leukemia?
alkylating agents (cyclophosphamide) or topoisomerase 2 inhibitors (etoposide, doxorubicin)
acute leukemia transformation
can arise from MDS, MPNs, and clonal marrow failure syndromes
most common childhood cancer?
ALL acute lymphocytic leukemia
how do leukemias arise?
marrow is constantly turning over cells in order to maintain normal blood cell pools. unfortunately gives more chances for mutations to occur. in acute leukemias, these occur at proliferative stage, blocking maturation somehow
who has an increased chance of getting acute leukemia?
children with inherited errors of dna repair
clinical definition of MDS
acquired, persistent reduction in circulating myeloid blood cell counts with abnormal blood cell morphology. indolent growth
MDS marrow morphology
hypercellular marrow, increased apoptosis. hypo granular granulocytic precursors. hypolobated, micromegakaryocytes. increased marrow blasts.
what types of mutations lead to acute leukemias?
nonrandom, multiple ones: recurrent chromosomal abnormalities and gene mutations seen.
APL (acute promyelocyte leukemia)
AML with t(15;17). fuses PML TF with retinoid acid receptor RARa, which then strongly binds DNA and recruits histone deacetylases, leading to transcription repression and maturational arrest.
treatment for APL
all-trans retinoid acid (ATRA). ligand for PML-RARa that restores transcription and induces cell maturation.
prognosis for ALL (childhood vs adult)
childhood ALL cured by intensive chemotherapy. Very difficult to cure in adults.
clinical symptoms of leukemia
fatigue, fever, infection, bleeding, lymph node enlargement, bone pain due to marrow expansion, cranial neuropathy (involvement of spinal fluid), testicular masses
clinical consequence of APL
highly dangerous bleeding risk
why is cancer in testes particularly bad?
chemotherapy can't gain access, must be radiated, which sterilizes
signs of leukemia
pallor, petechial rashes, splenomegaly, swollen gums
rare but serious complication of leukemia in which too many WBCs in circulation cause a leukothrombosis
how can you distinguish AML for ALL
cytologic abnormality in AML
Aeur rods in cytoplasm
aggregates of myeloperoxidase that form cytoplasmic needle like inclusions.
B lymphoid lineage immunophenotype
CD19, CD79a, Ig
T lymphoid lineage immunophenotype
myeloid lineage immunophenotype
CD13, 33, myeloperoxidase (MPO)
best predictor for treatment response and survival for acute leukemias?
favorable AML karyotypes
t(15;17) (PML treat with ATRA)