About the Condition

Description/definition:

Acute myeloid leukemia (AML) with inv(16)(p13q22) or t(16;16)(p13;q22) accounts for approximately 5–7% of all de novo AML cases. Molecularly, inv(16)/t(16;16) results in the juxtaposition of the myosin, heavy chain 11, smooth muscle gene (MYH11) at 16p13 and the core-binding factor, β subunit gene (CBFB) at 16q22, and creation of the CBFB-MYH11 fusion gene.

Inv(16)(p13.1q22) or t(16;16)(p13.1;q22) (inv(16)) is a defining cytogenetic abnormality of acute myeloid leukemia (AML), irrespective of the blast count according to the 2008 World Health Organization (WHO) classification.

AML with inv(16) typically presents with the morphology of acute myelomonocytic leukemia (AMMoL), associated with abnormal eosinophils, including immature forms with coarse, purple-violet granules and/or abnormal nuclear segmentation in the bone marrow aspirate; these abnormal eosinophils are thought to derive from the leukemic clone.

AML with inv(16) is often associated with secondary cytogenetic abnormalities, including trisomy 22, trisomy 8, del(7q), and trisomy 21.

Pathophysiology:

The inv(16)/t(16;16) results in fusion of the core-binding factor subunit beta (CBFB) gene at 16p22 and the myosin heavy chain 11 (MYH11) gene at 16p13, creating a new chimeric gene, CBFB-MYH11. At least 12 differently sized CBFB-MYH11 fusion transcripts have been reported, arising from multiple breakpoints in the MYH11 gene. The resultant CBFB-MYH11 fusion protein interferes with formation of the CBF complex and blocks the differentiation of hematopoietic cells.

Clinical presentation:

Patients present similarly to other types of acute leukemia.

Diagnosis:

  • Often presents with increased eosinophils by morphology in the bone marrow (BM) and/or peripheral blood.
  • Bone marrow showing:
    • Presence of abnormally large, coarse, purple-violet granules in the eosinophils and eosinophilic precursors.
    • +/- vacuolation or hypersegmentation in eosinophils.
    • +/- granulocytes may show dysplastic features such as cytoplasmic hypogranulation and/or abnormal segmentation.
  • Cytogenetic testing showed a 46 XY, inv(16)(p13.1q22),add(18)(p11.3)[5]/46,XY[15] karyotype.
  • FISH analysis using break-apart probes to confirm the presence of CBFB/MYH11 translocation.

Treatment and prognosis:

The AML with inv(16)(p13.1q22) or t (16;16)(p13.1;q22) is associated with a high rate of complete remission (CR) and favorable overall survival (OS) when treated with high-dose cytarabine.

Because of high remission rates after standard induction therapy and a long-term survival of 50% to 65%, inv(16) is categorized as favorable-risk AML within the 2017 European LeukemiaNet (ELN) genetic risk stratification and according to 2022 NCCN guideline.

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