Chromosomal abnormality of acute promyelocytic leukemia other than PML-RARA: a case report of acute promyelocytic leukemia with del(5q)

The recent study described a better outcome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic oxide compared to those treated with all-trans retinoic acid combined with conventional chemotherapy. The pivotal study indicated that favorable-risk acute promyelocytic leukemia patients can be cured without any cytotoxic chemotherapy. Even high-risk patients are treatable with cytotoxic agents. Acute promyelocytic leukemia does not develop only by the dedifferentiation caused by PML-RARA. A determined oncogene other than PML-RARA which promotes cell proliferation would be required.

We recently treated a 30-year-old Japanese female who achieved molecular remission with only the administration of all-trans retinoic acid. The patient’s leukemic clones concomitantly had a del(5q) aberrant chromosome with t(15;17) (q22;q12). The patient’s bone marrow cells indicated clonal evolution of the tumor cells expressing CD13dim, CD33+, CD117+, and lacking HLA-DR, CD34 and CD11b. A fluorescence in situ hybridization analysis detected PML-RARA fusion genes in the patient’s bone marrow specimens, leading to the diagnosis of acute promyelocytic leukemia.

A del(5q) is one of the characteristic chromosomal abnormalities observed in myelodysplastic syndrome. On the other hand, up to 40 % of acute promyelocytic leukemia cases are known to harbor the addition of a clonal cytogenetic abnormality. However, such a case acute promyelocytic leukemia with del(5q) would be rare, rather than myelodysplastic syndrome, consequently obtaining t(15;17). Which cytogenetic abnormalities, acute promyelocytic leukemia or myelodysplastic syndrome, came first is informative to make a clinical decision for the initial therapy. In this case, we speculated the PML-RARA translocation is an original pathogenesis and thereafter additional cytogenetic abnormalities (del(5q) and -6) common in myelodysplastic syndrome. All-trans retinoic acid lead the patient into molecular remission. We propose that an assessment of additional cytogenetic abnormality in acute promyelocytic leukemia would contribute to the clinical decisions regarding whether to treat disease with all-trans retinoic acid and cytotoxic agents. It would be of interest to know the extent of cytogenetic abnormality in the patients regarding to mixed leukemia. One or more additional cytogenetic abnormalities other than PML-RARA could account for the biological malignant grade and prognostic index.