Two Cases of Near-Tetraploidy in Acute Leukemias of Ambiguous Lineage

Acute leukemia of ambiguous lineage (ALAL) is a rare subtype of acute leukemias that does not show any clear evidence of differentiation along a single lineage [1]. Although both numerical and structural chromosomal abnormalities are commonly associated with acute and chronic hematologic malignancies, near-tetraploidy has been reported rarely (1.2% of AML cases) [2, 3]. Adult AML patients with tetraploidy are characterized by insensitivity to chemotherapy, low remission rates, and short survival periods (median, 4 months; range, from 0.1 to 32 months) [4]. There are very few cases described in the literature to determine whether there are any chromosomal abnormalities associated with ALAL [1, 2]. Here, we report 2 cases of adult ALAL with near-tetraploidy, representing the first such case reports in Korea. Case 1 involved a 63-yr-old Korean man. A complete blood cell (CBC) count at admission showed pancytopenia (hemoglobin level: 4.6 g/dL; white blood cell count: 3.17×10/L; absolute neutrophil count: 1.26×10/L; platelet count: 101×10/L). Immature cells were rare on the peripheral blood (PB) smear. The 500-cell differential count from the BM aspirate revealed that 70% of all nucleated cells were blasts with large sizes, high nuclear/cytoplasm (N/C) ratios, irregularly-shape nuclei, dispersed chromatin, distinct nucleoli, and basophilic cytoplasm that occasionally formed pseudopods (Fig. 1A). Cytochemical staining was negative for myeloperoxidase (MPO), periodic acid-Schiff (PAS), and nonspecific esterase (NSE). The BM biopsy specimen showed hypercellular marrow infiltrated by large immature cells. CD34-specific immunohistochemical staining showed strong positive staining for leukemic blasts. Flow cytometric analysis of the BM aspirate was performed with a 2-color Beckman Coulter Cytomics FC 500 flow cytometer (Beckman-Coulter, Fullerton, CA, USA). The result revealed that approximately 66% of the large cells were strongly positive for CD19 (99.0% of the gated blasts) and HLA-DR (98.7% of the gated blasts), and negative for all other myeloid (CD13, CD33, CD117, and MPO), B-lymphoid (CD20, CD22, and CD79a), Tlymphoid (CD2, CD3, CD5, CD7, and CD10), and terminal deoxynucleotidyl transferase (TdT) antigens. On the basis of morphologic features and immunophenotyping results of the BM aspirate, the patient was diagnosed with ALAL according to the 2008 WHO classification [1]. The result of conventional G-banding chromosomal analysis of the bone marrow cells was 89-93,XXYY,+X,-Y,-6,+7,-9,-14,-16,-18,-19,-20[cp6]/ 46,XY [14] (Fig. 1B). Interphase FISH using a DNA probe set specific for the AML1/ETO, BCR/ABL, MLL, PML/RARA, and CBFB genes (Vysis, Downers Grove, IL, USA) was performed according to the manufacturer’s protocols, and the result was nuc ish (RUNX1T1, RUNX1) ×4 [23/200]/(RUNX1T1, RUNX1) ×2 [173/200], (ABL ×3, BCR ×4) [20/200]/(ABL, BCR) ×2 [178/200] (MLL ×4) [21/200]/(MLL ×2) [175/200], (PML, RARA) ×4 [31/ 200]/(PML, RARA) ×2 [167/200], (CBFB×4) [37/200]/(CBFB