What is the difference between Acute Myeloid Leukemia (AML) and Acute Lymphoid Leukemia (ALL)?

Difference Between AML and ALL

Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) are fundamentally distinct malignancies that differ in their cell lineage of origin—AML arises from myeloid progenitor cells while ALL originates from lymphoid precursor cells (B-cell or T-cell lineage)—and this distinction is critical because it determines completely different treatment approaches, prognosis, and age distribution patterns. 1, 2

Cell Lineage and Origin

AML Characteristics

• AML originates from hematopoietic stem/progenitor cells of the myeloid lineage, leading to accumulation of immature myeloid cells (myeloblasts) in bone marrow, peripheral blood, and other organs 3, 2
• AML is the most common acute leukemia in adults, representing approximately 80% of adult acute leukemias, with median age at diagnosis in the 60s 1, 2
• Myeloblasts in AML typically show myeloperoxidase (MPO) positivity on cytochemical staining, which is a key distinguishing feature 1, 4

ALL Characteristics

• ALL arises from lymphoid progenitor cells, subdivided into B-cell lineage (75-88% of cases) and T-cell lineage (25% in adults, 12% in children) 1
• ALL represents 75-80% of acute leukemias in children but only 20% in adults, with median age at diagnosis of 13 years 1, 5
• Lymphoblasts in ALL are typically negative for myeloperoxidase and show characteristic markers like terminal deoxynucleotidyl transferase (TdT) 1, 4

Morphologic Differences

AML Morphology

• AML blasts tend to be larger with more abundant cytoplasm, lower nucleocytoplasmic ratio, and may contain Auer rods (pathognomonic for myeloid lineage) 4, 2
• Cytoplasm may show granules and the chromatin pattern is typically less condensed 4

ALL Morphology

• ALL blasts are characteristically small to medium-sized with high nucleocytoplasmic ratio, showing just a small cytoplasmic rim in many cases 4
• Cytoplasm tends to be moderately basophilic, usually agranular and free of vacuoles (except in L3/mature B-cell ALL which shows prominent vacuolation) 4
• Chromatin is more condensed than in AML and nucleoli tend to be indistinct 4

Immunophenotypic Markers

AML Markers

• AML expresses myeloid markers including CD13, CD33, CD117, and MPO 1
• CD34 and HLA-DR are frequently positive in less differentiated AML 2

ALL Markers

• B-cell ALL expresses CD19, CD22, CD79a, and commonly CD10 (common ALL antigen) 1
• T-cell ALL shows cytoplasmic or surface CD3, along with variable expression of CD1a, CD2, CD5, CD7 1
• TdT (terminal deoxynucleotidyl transferase) is characteristically positive in ALL but negative in mature B-cell ALL 1

Cytogenetic and Molecular Differences

AML Cytogenetics

• AML shows distinct recurrent abnormalities including t(8;21), inv(16), t(15;17) (acute promyelocytic leukemia), and complex karyotypes 2
• Molecular mutations in AML commonly involve FLT3, NPM1, CEBPA, IDH1/2, and TP53 2

ALL Cytogenetics

• ALL in children frequently shows hyperdiploidy (25%) and t(12;21)/TEL-AML1 (22%), both associated with favorable outcomes 1, 5
• Philadelphia chromosome t(9;22)/BCR-ABL is present in 25% of adult ALL (increasing to 40% in patients >50 years) but only 3% of childhood ALL, and confers poor prognosis 1, 5
• MLL rearrangements, particularly t(4;11), occur in 10% of adult ALL and 8% of childhood ALL with poor prognosis 1, 5

Diagnostic Approach

Key Diagnostic Steps

• Both require ≥20% blasts in bone marrow for diagnosis (with exceptions for specific recurrent cytogenetic abnormalities) 1, 5, 6
• Comprehensive flow cytometric immunophenotyping is essential to determine lineage (lymphoid vs myeloid) and cannot be reliably determined by morphology alone 1
• Morphology alone correctly distinguishes ALL from AML only 70-80% of the time, even by experienced morphologists 1

Critical Diagnostic Pitfall

• Myeloid-associated markers (CD13, CD33) may be expressed in up to 50% of ALL cases, and their presence does not exclude ALL diagnosis 1
• The rigid FAB criterion of <3% peroxidase-positive blasts for ALL diagnosis can be misleading—some poorly differentiated AML cases have <3% MPO-positive blasts, requiring immunophenotyping for definitive classification 4

Mixed Phenotype Acute Leukemia (MPAL)

• MPAL represents acute leukemias with ambiguous lineage, including bilineage (two distinct blast populations) or biphenotypic (single population expressing both lymphoid and myeloid markers) 1
• MPAL diagnosis requires comprehensive immunophenotyping following 2008 WHO criteria and represents a distinct diagnostic challenge 1

Age Distribution and Prognosis

Age Patterns

• ALL predominates in children with cure rates approaching 80% with current treatment regimens 1, 7
• AML is primarily an adult disease with much lower cure rates, particularly in older adults 3, 2

Prognostic Differences

• Pediatric ALL has dramatically better outcomes than adult ALL, partly due to different cytogenetic subtype frequencies (more favorable hyperdiploidy and TEL-AML1 in children) 1
• Adult AML prognosis varies widely based on cytogenetics, molecular markers, and patient age, with 5-year survival ranging from <10% to >70% depending on risk category 2

Clinical Presentation Overlap

• Both AML and ALL present with symptoms of bone marrow failure: fatigue, infections, bleeding/bruising, and constitutional symptoms (fever, night sweats, weight loss) 7, 6
• Both can cause organomegaly (hepatosplenomegaly, lymphadenopathy) and extramedullary involvement 6
• Clinical presentation alone cannot distinguish AML from ALL—laboratory and pathologic evaluation is mandatory 1, 6

Treatment Implications

• ALL requires 2-3 years of multi-agent chemotherapy with CNS prophylaxis, while AML typically involves shorter intensive induction and consolidation cycles 6
• The distinction between AML and ALL is absolutely critical for treatment selection, as regimens are completely different and non-interchangeable 1
• Patients should be treated at specialized centers with expertise in acute leukemia management 1, 5