Review Article

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

Table 1

Criteria defining acute leukemias according to current classifications.

Acute lymphoblastic leukemia Acute myeloid leukemiaAcute leukemias of ambiguous lineage and biphenotypic leukemia

WHO 2008B lymphoblastic leukemia/lymphomaAcute myeloid leukemia and related neoplasmsAcute leukemias of ambiguous lineage
(i) B lymphoblastic leukemia/lymphoma, NOS(i) Acute myeloid leukemia with recurrent genetic abnormalities(i) Acute undifferentiated leukemia
(ii) B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities AML with t(8;21)(q22;q22); RUNX1-RUNX1T1(ii) Mixed phenotype acute leukemia with t(9;22)(q34;q11.2); BCR-ABL1
 B lymphoblastic leukemia/lymphoma with (9;22)(q34;q11.2); BCR-ABL 1 AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11(iii) Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged
 B lymphoblastic leukemia/lymphoma with t(v;11q23); MLL rearranged APL with t(15;17)(q22;q12); PML-RARA(iv) Mixed phenotype acute leukemia, B-myeloid, NOS
 B lymphoblastic leukemia/lymphoma with t(12;21)(p13;q22) TEL-AML1 (ETV6-RUNX1)  AML with t(9;11)(p22;q23); MLLT3-MLL(v) Mixed phenotype acute leukemia, T-myeloid, NOS
 B lymphoblastic leukemia/lymphoma with hyperdiploidy  AML with t(6;9)(p23;q34); DEK-NUP214(vi) Provisional entity: natural killer (NK) cell lymphoblastic leukemia/lymphoma
 B lymphoblastic leukemia/lymphoma with hypodiploidy AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1
 B lymphoblastic leukemia/lymphoma with t(5;14)(q31;q32) IL3-IGH AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1
 B lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3); TCF3-PBX1 Provisional entity: AML with mutated NPM1
T lymphoblastic leukemia/lymphoma Provisional entity: AML with mutated CEBPA
(ii) Acute myeloid leukemia with myelodysplasia-related changes
(iii) Therapy-related myeloid neoplasms
(iv) Acute myeloid leukemia, not otherwise specified
 AML with minimal differentiation
 AML without maturation
 AML with maturation
 Acute myelomonocytic leukemia
 Acute monoblastic/monocytic leukemia
 Acute erythroid leukemia
  Pure erythroid leukemia
  Erythroleukemia, erythroid/myeloid
 Acute megakaryoblastic leukemia
 Acute basophilic leukemia
 Acute panmyelosis with myelofibrosis
(v) Myeloid sarcoma
(vi) Myeloid proliferations related to Down syndrome
 Transient abnormal myelopoiesis
 Myeloid leukemia associated with Down Syndrome
(vii) Blastic plasmacytoid dendritic cell Neoplasm

FABL1: lymphoblasts are usually smaller, with scanty cytoplasm and inconspicuous nucleoli M0: undifferentiated. Undifferentiated, large, agranular blasts; >90% blasts MPO−; SBB−
L2: lymphoblasts are larger, and they demonstrate considerable heterogeneity in size, prominent nucleoli and more abundant cytoplasmM1: acute myeloblastic, no maturation. Undifferentiated; >90% blasts; <10% promyelocytes/monocytes. MPO+;SSB+; PAS−
L3: lymphoblasts notable for their deep cytoplasmic basophilia, large, frequently display prominent cytoplasmic vacuolation, morphologically identical to Burkitt’s lymphoma cellsM2: acute myeloblastic with maturation. ≥30% and ≤89% blasts; >105 promyelocytes, myelocytes; <20% monocytic cells. MPO+; SSB+; PAS−
M3: acute promyelocytic-hypergranular type. >20% abnormal hypergranular promyelocytes; Auer rods common. MPO+; SSB+; PAS−
M3v: acute promyelocytic-hypogranular variant. Fine granularity of cytoplasm in promyelocytes; folded nuclei. MPO+; SSB+; PAS−
M4: acute myelomonocytic. ≥30% blasts on nonerythroid series; >20% but <80% monocytic cells; blood monocytes > / L; lysozyme >3 × normal. MPO+; NASDA+
M4eo: acute myelomonocytic with eosinophilia. >5% abnormal eosinophils with basophilic granules. MPO+; NASDA+ eosinophils; PAS+
M5a: acute monocytic. >80% of monocytic cells = monoblasts; rest are promonocytes/monocytes. MPO+; NASDA+
M5b: acute monocytic with differentiation. <80% of monocytic cells are monoblasts; rest are promocytes/monocytes. MPO+; NASDA+
M6: acute erythroleukemia. >30% of nonerythroid cells are blasts; >50% of marrow are erythroblasts. PAS+; ringed sideroblasts with iron stain
M7: acute megakaryoblastic. >30% of nonerythroid cells are megakaryoblasts; cytoplasmic blebs; myelofibrosis common. MPO−; SBB−; NASDA+ platelet MPO+ by EM

EGILScoring system for the definition of acute biphenotypic leukemias
Scoring lineages points
 2: B-lymphoid (CD79a, CD22, cyIgM) T-lymphoid (CD3) myeloid, (MPO)
 1: B-lymphoid (CD10, CD19), T-lymphoid (CD2, CD5), myeloid (CD13, CD33)
 0.5: B-lymphoid (TdT), T-lymphoid (TdT, CD7), myeloid (CD14, CD15, CD11b, CD11c)

NOS: not otherwise specified, MPO: myeloperoxidase, SSB: Sudan Black B, PAS: periodic acid-Schiff, EM: electron microscopy, NASDA: naphthol-ASD chloroacetate, TdT: Terminal deoxynucleotide transferase, and cy: cytoplasmic.