Inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)–ALK fusion gene in myeloid leukemia that developed in an elderly woman

Abstract

A 75-year-old woman presented with marked leukocytosis; the white cell count was 143.6 × 10³/μL with 38.6 % monocytes and 13.6 % immature granulocytes, including blasts. Bone marrow (BM) aspirate smears showed >90 % cellularity with hyperplasia of myeloid-lineage cells, 14.6 % monocytes, and 32.1 % blasts. The granulocyte series showed a range of dysplastic morphologies. The rate of peroxidase positivity was 51.5 %. CD36+ cells with monocytic differentiation comprised 64.6 % mononuclear cells. Metaphase spreads obtained from the BM revealed an aneuploid karyotype with -7 and a submetacentric marker chromosome derived from chromosome 2, which was determined to be inv(2)(p23q13) by fluorescence in situ hybridization using the Vysis ALK probe. RAN-binding protein 2 (RANBP2)-ALK fusion mRNA was confirmed by reverse transcriptase-mediated polymerase chain reaction and nucleotide sequencing. High-sensitivity anti-ALK immunohistochemistry of a BM biopsy specimen demonstrated nuclear membrane staining of leukemia cells. As the leukemia showed features of chronic myelomonocytic leukemia, the patient was treated with standard daunorubicin-cytarabine followed by azacitidine, leading to the durable suppression of leukemia progression. These findings suggest that inv(2)(p23q13)/RABBP2-ALK defines a small subset of myeloid leukemia characterized by differentiation to monocytes and sharing features of myelodysplastic syndrome/myeloproliferative neoplasm.