Types of Acute Leukemia
Acute leukemia is classified into three major categories: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and acute leukemia of ambiguous lineage (ALAL), with each category further subdivided based on genetic, immunophenotypic, and morphologic features. 1
Major Categories
Acute Myeloid Leukemia (AML)
AML is defined by ≥20% myeloid blasts in peripheral blood or bone marrow, encompassing cells of granulocytic, monocyte/macrophage, erythroid, megakaryocytic, and mast cell lineages. 1 The WHO classification system incorporates cytogenetic data, molecular genetics, immunophenotype, and clinical information to define clinically significant disease entities. 1
Key AML subtypes include:
Acute Promyelocytic Leukemia (APL): Characterized by t(15;17)(q22;q12) translocation creating the PML-RARA fusion gene, representing approximately 10% of all AML cases with a median age of 44 years. 2 This is a medical emergency due to severe coagulopathy and hemorrhage risk. 2
Core Binding Factor AML (CBF-AML): Includes AML with t(8;21)(q22;q22), inv(16)(p13.1q22), or t(16;16)(p13.1;q22), representing favorable-risk disease. 1
AML with normal karyotype: Intermediate-risk group where molecular markers (FLT3, NPM1, CEBPα mutations) determine prognosis. 1
AML with complex karyotype or monosomies: Unfavorable-risk disease. 1
Myeloid leukemia associated with Down syndrome: A distinct WHO entity with unique clinical and biological features, including transient abnormal myelopoiesis in newborns. 3
Acute Lymphoblastic Leukemia (ALL)
ALL is divided into B-lymphoblastic leukemia/lymphoma and T-lymphoblastic leukemia/lymphoma based on lineage commitment. 1
Diagnostic criteria:
When a mass is present with ≥25% bone marrow lymphoblasts, diagnose as lymphoblastic leukemia rather than lymphoma. 1
With <20% bone marrow blasts but presence of known recurring cytogenetic abnormalities associated with ALL, the diagnosis of B-lymphoblastic leukemia/lymphoma can still be made. 1
Important distinction: Burkitt lymphoma/leukemia is NOT classified as B-ALL, as it represents a mature B-cell neoplasm. 1
Acute Leukemia of Ambiguous Lineage (ALAL)
This category encompasses leukemias that either fail to show evidence of lineage commitment or demonstrate commitment to multiple lineages. 1
Mixed Phenotype Acute Leukemia (MPAL):
Formerly called "bilineal" or "biphenotypic" acute leukemia, now collectively termed MPAL. 1
Specific genetic abnormalities like t(8;21) generally exclude MPAL classification, with exceptions for BCR-ABL1 fusion and MLL rearrangements. 1
For BCR-ABL1-positive cases meeting criteria for multiple lineages, diagnose as MPAL with t(9;22)(q34;q11.2) after excluding CML blast phase. 1
Recent genomic studies reveal MPAL shows mutations common to both AML and ALL, with T-/myeloid MPAL overlapping with early T-cell precursor lymphoblastic leukemia. 4
Natural killer cell lymphoblastic leukemia/lymphoma:
Provisional entity with unclear defining phenotype. 1
Consider when blasts express CD56 with immature T-associated antigens (CD7, CD2) without B or myeloid antigens and no T-cell receptor gene rearrangement. 1
Most cases previously designated as "blastic NK-cell leukemia/lymphoma" are now recognized as blastic plasmacytoid dendritic cell neoplasms. 1
Clinical Implications
Common pitfall: The different treatment regimens for AML versus ALL make accurate lineage assignment critical—ALAL presents both diagnostic and therapeutic challenges. 4 AML typically requires intensive chemotherapy with cytarabine and anthracyclines, while ALL uses different regimens. 5
Risk stratification in AML is governed by karyotype and molecular features, with APL requiring immediate ATRA therapy upon clinical suspicion even before genetic confirmation. 1, 2 Age, initial leukocyte counts, and whether the leukemia is de novo or secondary are critical prognostic factors. 1