Characteristics of hematologic malignancies with coexisting t(9;22) and inv(16) chromosomal abnormalities

Abstract

BackgroundThe coexistence of t(9;22)(q34;q11.2) and inv(16)(p13q22) chromosomal abnormalities is extremely uncommon, and only a small number of such cases have been reported. Here, we characterized 7 cases of hematologic malignancy exhibiting t(9;22) and inv(16) coexistence.MethodsWe reviewed the cytogenetic data for hematologic malignancies treated at the Catholic Blood and Marrow Transplantation Center between January 2004 and June 2013. We identified 7 cases exhibiting t(9;22) and inv(16) coexistence. In addition, we analyzed mutations in the IKZF1, NPM1, FLT3, N-RAS, K-RAS, c-KIT, and TP53 genes.ResultsFour cases of chronic myelogenous leukemia (CML; 1 chronic phase, 2 accelerated phase, and 1 blast phase) and 3 cases of acute myeloid leukemia (AML; 1 de novo and 2 therapy-related) were identified. The percentages of circulating blasts and bone marrow eosinophils were higher in AML cases than in CML cases (53% vs. 5% and 30% vs. 5.5%, respectively). The proportions of each chromosomal abnormality were used along with follow-up karyotyping results to identify secondary changes. In BCR/ABL, a p210 fusion transcript was associated with CML, whereas a p190 fusion transcript was associated with AML. One patient with AML harbored 2 mutations: c-KIT D816V and TP53 E11Q. All patients except 1 with CML blast phase sustained clinical remission after treatment, which included an imatinib mesylate regimen.ConclusionThis study shows that observations of bone marrow morphology, initial and follow-up cytogenetic studies, and karyotyping of BCR/ABL1 and CBFB/MYH11 provide valuable information for characterizing hematologic malignancies exhibiting t(9;22) and inv(16) coexistence.

BCR-ABL + acute myeloid leukemia: are we always dealing with a high-risk disease?

“…Regarding the outcome of this favorable subgroup of patients with BCR-ABL 1 AML, it is surprising that many of these patients were long-term survivors, although they had been treated with chemotherapy 6 TKI alone (without allogeneic stem cell transplantation). 5,[8][9][10] These data clearly suggest that the presence of BCR-ABL did not alter the overall favorable outcome in these subgroups ( In this patient cohort, which was in part recently published, 13 a 2-year overall survival of 34% was observed. Interestingly, the survival did not substantially differ between patients achieving a CR before HSCT and patients who did not (34.7% vs 33.5%; Figure 1).…”

Coexistence of Recurrent Chromosomal Abnormalities and the Philadelphia Chromosome in Acute and Chronic Myeloid Leukemias: Report of Five Cases and Review of Literature

“…AML with Inv(16) and t(9;22) is extremely rare. Clonal evolution appearing in the process of CML acceleration or AML progression has been more frequently reported in the literature [27,28,29,30,31,32]. The case in the present study did not have a history of CML, and was initially diagnosed with AML-M5.…”

t(9;22) as secondary alteration in core‐binding factor de novo acute myeloid leukemia

“…The reported FAB subtype is always M4/M4Eo, except for one case, which was M1 [5], and all patients presented with characteristic inv(16)(p13.1q22) and t(9;22)(q34;q11.2). Additional cytogenetic abnormalities were reported in four of the patients [4,[8][9][10]. The produced BCR-ABL1 chimeric protein was the p190 variant in all cases except one, which was positive for the p210 variant [8].…”

“…To date, there are only 11 cases described in the literature in which the t(9;22) definitely represents a secondary event in an inv(16) AML [1][2][3][4][5][6][7][8][9][10]. The reported FAB subtype is always M4/M4Eo, except for one case, which was M1 [5], and all patients presented with characteristic inv(16)(p13.1q22) and t(9;22)(q34;q11.2).…”

“…The availability of tyrosine kinase inhibitors (TKI) specifically targeting BCR-ABL1 could potentially have an impact on the outcome of patients with CBF AML and secondary t(9;22), as suggested by anecdotal published cases [3,6,7,9,10]. The choice of a second or third generation TKI should balance the toxicity profile, the availability of the drug, and the efficacy data extrapolated from in vitro studies and from other disease settings.…”