Leukemia Study Pack: Acute and Chronic Leukemias Flashcards

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Chronic myeloid leukemia

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A BCR/ABL-positive chronic myeloproliferative malignancy of the pluripotent hematopoietic stem cell characterized by excessive accumulation of granulocytic-lineage cells in bone marrow, blood, liver, and spleen. It is defined by the t(9;22) translocation producing the Philadelphia chromosome and can progress to a blastic (acute) crisis.

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Philadelphia chromosome

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A shortened chromosome 22 created by reciprocal translocation t(9;22) that fuses BCR and ABL genes, producing an oncogenic BCR/ABL fusion protein. It is the hallmark genetic lesion of chronic myeloid leukemia (CML) and has diagnostic and therapeutic implications.

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BCR/ABL fusion

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An abnormal fusion gene created by t(9;22) that encodes a constitutively active tyrosine kinase driving uncontrolled proliferation of myeloid cells. Targeted therapies (tyrosine kinase inhibitors) aim at inhibiting this oncoprotein.

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Leukocytosis in CML

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Marked elevation of white blood cell count, often with counts greatly exceeding normal (can be above $500\times10^9$/L), with predominance of mature neutrophils and a left shift. Blast percentage remains below 20% in the chronic phase.

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Alkaline phosphatase in leukocytes

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In CML, leukocyte alkaline phosphatase (LAP) activity is typically decreased, which helps distinguish CML from other myeloproliferative disorders where LAP may be elevated. LAP testing is part of the laboratory workup when differentiating causes of leukocytosis.

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Bone marrow transplantation

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The only potentially curative treatment for some leukemias, including advanced CML in select patients. Successful outcome depends on donor match (preferably a close relative) and early disease stage at transplantation.

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Malignant diseases of leukocytes

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Broad group of hematopoietic malignancies (formerly hemoblastoses) characterized by clonal transformation, uncontrolled proliferation, and accumulation of malignant leukocytes at various stages of hematopoiesis. They include leukemias (blood), lymphomas (lymph nodes), and myelomas (bone marrow).

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Acute vs chronic leukemias

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Acute leukemias show many immature blasts, rapid progression, and require urgent therapy, while chronic leukemias have more mature cells, a slower course, and can transform into acute leukemia. Chronic forms may be asymptomatic for long periods but still risk progression.

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Risk factors for leukemias

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Known risk factors include genetic mutations and chromosomal abnormalities, ionizing radiation, chemical exposures (e.g., benzene), certain chemotherapeutic agents, and chronic viral infections. Many cases, however, have no clearly identifiable cause.

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Acute leukemia definition

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A clonal malignant disorder of hematopoietic stem cells marked by accumulation of large numbers of immature, nonfunctional blasts in bone marrow and blood. Without treatment, it is rapidly fatal within months.

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Diagnostic blast criteria

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Diagnosis of acute leukemia is based on blast percentage in bone marrow: more than 20% blasts for AML (per slides) and more than 25% for ALL in some contexts. Additional tests (cytochemistry, flow cytometry, cytogenetics) confirm lineage and molecular features.

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Cytogenetic testing

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Detects chromosomal abnormalities (translocations, inversions, deletions, duplications) that define subtypes, influence prognosis, and guide targeted therapy. Examples include t(15;17) in APL and t(8;21) in AML.

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FAB classification

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An older morphological classification for acute leukemias: ALL subtypes L1–L3 based on lymphoblast features, and AML subtypes M0–M7 based on myeloid differentiation and cytochemical findings. It remains useful for describing morphology alongside WHO categories.

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WHO classification

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Modern classification based on lineage (B-ALL, T-ALL) and specific genetic/morphologic criteria for AML (e.g., AML with recurrent genetic abnormalities, therapy-related AML). It integrates molecular genetics, morphology, and clinical features.

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Gumprecht shadows

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Fragile, disrupted lymphocyte nuclei seen in peripheral blood smears of CLL patients, representing smudge cells characteristic of the disease. Their presence supports the peripheral smear diagnosis of CLL but is not pathognomonic.

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Chronic lymphocytic leukemia

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A slow-growing monoclonal B-lymphocyte malignancy that accumulates in blood, bone marrow, spleen, liver, and lymph nodes, often affecting older adults. Many patients are asymptomatic initially and require treatment only when symptomatic or progressive.

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Prognostic markers in CLL

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Markers such as CD38 expression and ZAP-70 tyrosine kinase overexpression are associated with worse prognosis and shorter survival. Multiple gene mutations also correlate with disease course and therapy response.

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Splenomegaly in CLL

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Spleen enlargement is common in CLL due to lymphocyte accumulation and contributes to abdominal fullness and early satiety. It also reflects disease burden and is used in staging.