Analysis of acute myeloid leukemia in Korean patients with sole trisomy 6.

Abstract

Autosomal as a sole cytogenetic change has been described in several hematologic malignancy cases, but the number of reports on the association between specific morphologies and individual structural cytogenetic abnormalities are few [1]. Trisomy 8 is the most common abnormality in myeloproliferative neoplasms (MPN), MDS, MDS/MPN and AML, and 4, 9, 11, 13, and 21 have been reported to be associated with myeloid disorders [1, 2]. Here, we describe three patients with and show that 6 is the sole clonal cytogenetic bone marrow abnormality. The patients were adults without previous hematologic disorders, and were initially diagnosed with M1, M2, and M4, according to the French-American-British (FAB) classification. These patients received chemotherapy with or without allogenic peripheral blood stem cell transplantation (PBSCT), and showed variable clinical outcomes. The first case of sole 6 abnormality was reported in a patient with aplastic anemia (AA) [2]. The other reports showed that 6 was associated with hypoplastic bone marrow, dyserythropoiesis and prior to hypocellular marrow with MDS [3, 4, 5]. To establish a relationship between the clonality of and a single 6 abnormality, we searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) with combinations of the search terms AML and trisomy Subsequently, we identified ten reports describing 18 cases of presenting with 6 as the sole karyotypic abnormality. The laboratory findings and clinical features, including those of the three cases reported here, and those of previously reported cases are summarized in Table 1. Including our three cases, there were 10 female and 11 male patients, including 3 children and 1 infant. The mean age was 41.4 yr, with a range of 22 months to 82 yr. Their bone marrow (BM) cellularity was variable, but it showed a hypo- to normocellular tendency. Although some cases were reported without the results of a complete blood count (CBC), we found six cases of cytopenia in a single cell line (five cases of thrombocytopenia and one case of anemia), three cases of cytopenia in two cell lines (both anemia and thrombocytopenia), and one case of pancytopenia. Leukocytosis was found in six of the 11 cases with CBC results. There were four cases each of M1 and M2, three cases of M4, two cases of M5, and one case of M7 diagnosed according to FAB criteria; four cases of the 21 were diagnosed as having without additional categorization. Case number (No.) 10 was suspicious for AML-M3, but no rearrangement of t(15;17)(q22;q12) was identified, so it was not presumed to be AML-M3. Case No.14 was reported as relapsed from refractory anemia with excess of blasts in transformation (RAEB-t), but we reclassified the case as with myelodysplasia-related changes according to the 2008 WHO classification. Case No. 20 was similarly reclassified as with myelodysplasia-related changes owing to MDS, according to the 2008 WHO classification. This patient initially showed hypocellular BM with mild dysplastic changes and 47,XX,+6[14]/46,XX[6], and then experienced transformation into 15 months later with an increase in the proportion of 6 cells and 47,XX, +6[39]/46,XX[1]. Mohamed et al. [5] mentioned that the increase in blasts was associated with an increase in the proportion of 6 cells. In our three cases, case No. 1; 81% of blasts with 47,XY,+6[20], No. 2; 60% of blasts with 47,XX,+6[20] and No. 3; 50% of blasts with 47,XY,+6[4]/46,XY[16] showed that there were no direct correlations between the number of blasts and the percentage of abnormal metaphases. Most patients with this abnormality received chemotherapy. Bone marrow transplantation (BMT) or PBSCT was performed in three of the cases. The survival from the time of diagnosis was variable and ranged from one month to longer than 58 months. Table 1 The laboratory findings and clinical features in with sole 6 We reported three Korean patients with with a particular genetic abnormality, showing the presence of 6 as the sole clonal cytogenetic abnormality of BM cells and reviewed other cases of with 6 in the literature. Although other studies and literature reviews that have attempted to establish the clinicopathologic and clinicohematologic characteristics of with sole trisomies 4, 8, 11, and 21 [6, 7, 8, 9] were found, we could not identify any correlation between morphology or prognosis and 6. In view of the literature, we suggest that 6 is a nonrandom clonal cytogenetic marker of AML, and it may sometimes be the result of transformation from other myeloid disorders. Further studies to establish the clonality of with sole 6 are needed.