How do you differentiate between acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) based on peripheral smear and bone marrow findings?

Acute leukemias are primarily diagnosed through a combination of complete blood count (CBC) with differential, peripheral blood smear examination, and bone marrow aspiration and biopsy. These tests help to identify the presence and characteristics of abnormal blast cells, which are crucial for differentiating ALL from AML.

Peripheral Smear Findings

The peripheral blood smear provides the first crucial clues for distinguishing ALL from AML.

• Blast Morphology: Examination under a microscope reveals the morphological features of the blast cells, which can often guide the initial differentiation.
• Other Cell Lines: The presence or absence of other immature or abnormal cells can also be indicative.

Bone Marrow Findings

Bone marrow aspiration and biopsy are essential for confirming the diagnosis, assessing the percentage of blasts, and providing detailed insights into the cellular characteristics and architectural changes. A diagnosis of acute leukemia typically requires more than 20% blast cells in the bone marrow.

Key Differentiating Features: ALL vs. AML

The following table summarizes the key features differentiating ALL and AML based on peripheral smear and bone marrow findings:

Feature	Acute Lymphoblastic Leukaemia (ALL)	Acute Myeloid Leukaemia (AML)
Cell Origin	Lymphoid progenitor cells (B-lymphoblasts or T-lymphoblasts)	Myeloid progenitor cells (myeloblasts, monoblasts, erythroblasts, megakaryoblasts)
Peripheral Smear: Blast Morphology	Smaller blasts (L1, L2, L3 types based on FAB classification). Scanty to moderate cytoplasm. Nucleoli are usually indistinct or small. Nuclear chromatin is often condensed. Cytoplasmic granules typically absent. Auer rods are generally absent.	Larger blasts. Abundant cytoplasm. Prominent, often multiple nucleoli. Nuclear chromatin is finely dispersed. Cytoplasmic granules often present (e.g., in M2, M3, M4). Auer rods are often present (pathognomonic for AML, particularly in M1-M4 subtypes).
Bone Marrow Findings: Blast Percentage	Typically >20% lymphoblasts.	Typically >20% myeloblasts (exceptions exist for specific genetic subtypes, e.g., t(8;21), inv(16), PML-RARA, where blast percentage can be lower).
Bone Marrow Findings: Erythropoiesis and Megakaryopoiesis	Normal or slightly reduced. Dysplasia is generally not prominent.	Often dysplastic (abnormal maturation) and reduced. Can sometimes involve erythroid or megakaryocytic lineages primarily (e.g., Pure Erythroid Leukemia, Acute Megakaryoblastic Leukemia).
Cytochemical Stains	Myeloperoxidase (MPO): Negative. Sudan Black B (SBB): Negative. Non-specific Esterase (NSE): Negative (except in some T-ALL variants). Periodic Acid-Schiff (PAS): May show block positivity (granular or chunky positivity) in some ALL.	Myeloperoxidase (MPO): Positive (especially in myeloblasts). Sudan Black B (SBB): Positive (correlates with MPO). Non-specific Esterase (NSE): Positive in monoblasts and promonocytes (e.g., in M4, M5).
Immunophenotyping (Flow Cytometry)	Expresses lymphoid markers (e.g., CD19, CD20, CD22 for B-ALL; CD2, CD3, CD5, CD7 for T-ALL). May express TdT (Terminal deoxynucleotidyl transferase).	Expresses myeloid markers (e.g., CD13, CD33, CD117, MPO). May express CD14, CD64 (monocytic differentiation). TdT is typically negative.
Cytogenetics and Molecular Genetics	Common abnormalities: t(9;22) (Philadelphia chromosome), t(12;21), KMT2A rearrangements. These have significant prognostic implications.	Common abnormalities: t(8;21), inv(16), t(15;17) (PML-RARA in Acute Promyelocytic Leukemia), FLT3-ITD, NPM1 mutations. These are critical for risk stratification and targeted therapy.
Age of Onset	Most common in children (ages 2-5) and adults over 50.	Most common in adults over 65 years. Also occurs in children.

Advanced Diagnostic Techniques

While peripheral smear and bone marrow examination with cytochemistry provide initial differentiation, modern diagnostics leverage sophisticated techniques for definitive classification and prognostic assessment:

• Flow Cytometry: This technique is crucial for immunophenotyping, allowing for precise identification of cell lineage (myeloid vs. lymphoid) and subtype based on surface and intracellular markers.
• Cytogenetics: Karyotyping identifies chromosomal abnormalities (e.g., translocations, deletions), which are highly specific for certain ALL and AML subtypes and carry significant prognostic value.
• Fluorescence In Situ Hybridization (FISH): Used to detect specific genetic rearrangements when routine karyotyping is inconclusive or for rapid detection of recurrent aberrations.
• Molecular Genetics (PCR, NGS): Identifies gene mutations (e.g., FLT3, NPM1 in AML; BCR-ABL1 in ALL) that guide treatment decisions, particularly for targeted therapies, and predict disease course.