Three Novel Clonal Non-Characteristic Chromosome Aberrations in Acute Myeloid Leukemia Resembling Acute Promyelocytic Leukemia

Abstract 4912

We report here three acute myeloid leukemia cases with novel clonal non-characteristic chromosome aberrations and morphologically resembling acute promyelocytic leukemia (APL).

Case No.1: A 57-year-old woman came with mucosal bleeding, ecchymoses, and fever. Blood tests showed hemoglobin (Hb) of 9.3g/dL, platelet count (Plt) of 29×10⁹/L and white blood cell count (WBC) of 1.3×10⁹/L. D-dimer was 3.6ug/ml and Fibrin degradation product (FDPs)>5ug/ml. Bone marrow (BM) morphology showed 91% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of peripheral blood (PB) blasts showed 83% positive for CD9, CD13, CD15, CD33, CD64, CD117 and negative for CD34, HLA-DR and B, T-cell markers. PML-RARA and t(15;17) negative but clonal t(1;16)(q44;q22) positive. The patient was initially treated with all-trans retinoic acid (ATRA), As₄S₄ and mitoxantrone and then switched to harringtonine and ara-C treatment but couldn't get remission.

Case No.2: A 39-year-old woman came with asthenia, mucosal bleeding and ecchymoses. Blood tests showed Hb of 10g/dL, Plt of 49×10⁹/L and WBC of 6.2×10⁹/L. D-dimer >20ug/ml and FDPs >20ug/ml. BM morphology showed 84% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of PB blasts showed 76% positive for CD13, CD33, CD64, CD117, cMPO and negative for CD9, CD34, HLA-DR and B, T-cell markers. PML-RARA and t(15;17) negative but clonal t(7;17)(p10;q10) positive. The patient was initially treated with ATRA and As₄S₄ and mitoxantrone but couldn't get a good response. He was then switched to idarubicin and ara-C treatment and got partial response. He is now waiting for allogeneic hematopoietic stem cell transplantation.

Case No.3: A 62-year-old man came with asthenia. Blood tests showed Hb of 68 g/dL, Plt of 61×10⁹/L and WBC of 3.3×10⁹/L. D-dimer was 10.2ug/ml and FDPs was not tested. Bone marrow (BM) morphology showed 63.5% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of Bone marrow showed 71.2% positive for CD13, CD15, CD33, CD117, cMPO and negative for CD34, HLA-DR,and B, T-cell markers. PML-RARA and t(15;17) negative but clonal (47,XY,+mar1) positive. The patient was initially treated with ATRA and As₄S₄ but couldn't get a good response. He was then swiched to Daunorubicin and ara-C treatment and got partial remission.

APL should be distinguished from other subtypes of acute myeloid leukemia (AML) because of the increased risk of disseminated intravascular coagulation (DIC) and its response to ATRA and arsenic compounds. Some cases of AML seem morphologically similar to APL but lack the characteristic t(15;17) or other RARA-related translocations, and they generally didn't response to ATRA and arsenic compounds treatment. The 3 cases reported here reiterate the lack of specificity of morphologic and Immunophenotyping findings in APL-like AMLs. Karyotypic analysis, as well as FISH and RT-PCR, must be conducted on these cases to rule out APL and other chemotherapy regimens should be considered. APL-like AMLs that do not demonstrate RARA-related translocations may constitute a heterogeneous population of AML with diverse clonal non-characteristic chromosome aberrations, and the molecular mechanisms is worthy of further study.