New Translocation (7:17) In Variant Acute Promyelocytic Leukemia With ATRA Resistance

Acute promyelocytic leukemia (APL) is characterized by pathologic promyelocytes, chromosomal translocations t(15:17) (q22; q21) and clinical and cytological response to all-transretinoic acid (ATRA). A significant minority of patients with APL have variant translocations involving RARα gene with a different partner, not involving PML. These APL variant translocations may or not respond to ATRA treatment.

A routine laboratory evaluation, before minor surgery, revealed leukocytosis, thrombocytopenia and blasts presence in peripheral blood (PB), in an otherwise asymptomatic 70-year-old man. He had a previous history of hypertension, dyslipidemia, ischemic heart disease, double coronary bypass and prostatectomy for non-malignant prostatic hypertrophy.

Peripheral blood (PB) count: hemoglobin concentration 12g/dL, platelet count: 21x10⁹/L and white blood cell count (WBC): 35x10⁹/L. Peripheral blood smear: myelemia exhibiting 74% blasts (including myeloid blast and promyelocytes) with fine chromatin pattern, heterogeneous and frequently convoluted nuclei and one to three prominent nucleoli. The cytoplasm of these cells was basophilic with scanty purple granules. No Auer rods were found. The basic coagulation tests were normal(INR, APTT and fibrinogen) but D Dimer was 33.87 µg/ml. Normal biochemistry was shown, except for GGT 85 U/L and lactate dehydrogenase 2244 U/L.

Bone marrow (BM) aspirate was unsuccessful (”dry tap”) but the bone trephine revealed an infiltration of 80% myeloid blasts. Cytochemistry: myeloperoxidase stain was deeply positive and chloroacetate and non-specific esterase stains were negative. Flow cytometry immunophenotype on PB was consistent with AML, likely M3 leukemia, with an atypical phenotype (MPO+, CD117^+low, CD34⁺, CD13⁺⁺, CD45⁺, CD15^-,CD133^-, CD33⁺, HLA-DR^{+low het} , CD5^-, CD7^-, CD11b^- , CD56^+het, CD10^-, CD8^- ,CD4^-, CD45RA⁺, CD19^-, CD2^-, Glya^-, CD71^+low, CD38^-, CD1a^-, CD41^-, CD14^-).

The analysis of the PML/RARα fusion gene, according to standard protocols, was negative. FISH studies showed 2 PML signals and 3 RARα copies, suggesting a possible variant rearrangement of this gene. FISH and molecular biology did not detect transcript for t(15:17), (5:17) or (11:17); so RARα was translocated with a strange partner.

Suspecting of a variant APL, the patient was treated with ATRA plus Idarrubicin. After 4 weeks treatment, deep neutropenia was observed but no granulocytic maturation. That suggested us resistance to ATRA. Thus, we changed the treatment to a classical induction scheme for AML. The patient attained cytologic remission, which he mantains so far with conventional chemotherapy.

Karyotype study was subsequently performed, identified an unbalanced rearrangement between 7q and 17q. Currently, we are identifying and sequencing the fusion partner of RARα.

We report a novel case of variant acute promyelocytic leukemia with the karyotype der (7) t(7;17) (q11;q21). The morphology of PB and BM was critical for initial diagnosis and treatment decisions.

No relevant conflicts of interest to declare.