AML with t(8;21) (q22;q22)

Epidemiology and Etiology:

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Common sites:

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Gross features:

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Histologic features:

· mostly found in M2 (>90% of t(8;21)) (10% of M2)

· Also found in M1 (5% of M1) and rarely in M4

· neutrophil lineage differentiation

· large blasts with abundant basophilic cytoplasm

· numerous azurophilic granules often

· Auer rods frequently

· perinuclear clearing or hofs

· smaller blasts predominantly in the peripheral blood

· promyelocytes, myelocytes, and mature neutrophils with variable dysplasia in the BM

· monocytic component miminal or absent

· dysplasia of other cell lines is uncommon

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Immunophenotype:

Marker:

Sensitivity:

Specificity:

• blast population: CD34+, HLA-DR+, MPO+, CD13+, CD33 (weak)
• granulocytic population: CD15 and/or CD65
• maturation asynchrony sometimes (ex. co-expressing CD34 and CD15)
• lymphoid markers frequently positive: CD19, PAX5, CD79a
• eosinophilic precursors frequently increased
• no cytological or cytochemical abnormalities like those of chr 16 abnormalities
• TdT+ in some (weak)
• CD56+ in some (may have adverse prognosis)

Molecular features:

· RUNX1 (AML1) (CBFA):

· One of the heterodimeric components of core binding factor (CBF), along with CBFB

· CBF transcription factor is essential for haematopoiesis

· AML1/ETO (RUNX1-RUNX1T1) fusion gene:

· levels can be detected and quantitated with Q-RT-PCR

· transcriptional repression of normal RUNX1 target genes

· additional chromosome abnormalities (>70%)

· loss of a sex chromosome

· del(9)(q) with loss of 9q22

· Secondary mutations often present:

· KRAS

· NRAS

· KIT (may have adverse prognosis) (20-25%)

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Other features:

· Good prognosis:

· associated with the highest probability of remaining in complete remission at 5 years

· Good response to chemo

· High complete remission rate

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References:

· Swerdlow. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. 4th ed. WHO Publications; 2008.

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