Characteristics of t(8;21) acute myeloid leukemia (AML) with additional chromosomal abnormality: concomitant trisomy 4 may constitute a distinctive subtype of t(8;21) AML

Abstract

and 9 Tokura Hospital, Kyoto, Japan t(8;21)(q22;q22) is the most frequently observed karyotypic abnormality associated with acute myeloid leukemia (AML), especially in FAB M2. Clinically, this type of AML often shows eosinophilia and has a high complete remission rate with conventional chemotherapy. t(8;21) AML is also frequently associated with additional karyotypic aberrations, such as a loss of the sex chromosome; however, it is unclear whether these aberrations change the biological and clinical characteristics of t(8;21) AML. To investigate this issue, 94 patients with t(8;21) AML were categorized according to their additional karyotypic aberrations, which were detected in more than three cases, and then morphologic features, phenotypes, expression of cytokine receptors, and clinical features were compared to t(8;21) AML without other additional aberrant karyotypes. t(8;21) AML with loss of the sex chromosome and abnormality of chromosome 9 were found in 27 cases (29.3%) and 10 cases (10.6%), respectively; however, no differences were observed from the t(8;21) AML without other additional karyotypes in terms of morphological and phenotypic features. There was also no significant difference in the clinical outcome among these three groups. On the other hand, trisomy 4 was found in three cases (3.2%) and these cells showed low expressions of CD19 (P = 0.06) and IL-7 receptor (P = 0.05), and high expressions of CD33 (P = 0.13), CD18 (P = 0.03), and CD56 (P = 0.03) when compared to t(8;21) AML without additional karyotypes. Moreover, all three t(8;21) AML cases with trisomy 4 did not show eosinophilia in their bone marrow and died within 2.4 years. These observations suggest that additional karyotypic aberration, t(8;21) with trisomy 4 is rare, but it may constitute a distinctive subtype of t(8;21) AML.

Acute myeloid leukemia harboring t(8;21)(q22;q22): a heterogeneous disease with poor outcome in a subset of patients unrelated to secondary cytogenetic aberrations

“…Notably, the loss of a sex chromosome and deletion of chromosome 9q are most common and their impact on survival is controversial. 1,5,15,[17][18][19][20] In this study, we confirmed that the loss of a sex chromosome and del(9q) were common, in 22 (39%) and six (11%) cases, respectively, and these aberrations did not correlate with poorer clinical outcome. These results are in keeping with the observations by other investigators who had 4100 cases in their respective study series.…”

“…Exclusion of refractory and relapsed patients from the analysis yielded a similar result (P ¼ 0. 19) Comparison between patients with a complex karyotype and those with isolated t(8;21) also found no significant difference in survival for the entire cohort (P ¼ 0.91) (Figure 3) or newly diagnosed patients (P ¼ 0.25). Relapsed/refractory Idarubicin+ara-C 17 Daunorubicin+ara-C 1 Allo-BMT 6…”

“…Loss of a sex chromosome and del(9q) have been reported to adversely, 16 favorably 1,17,18 or marginally affect the survival of patients with t(8;21). 5,15,19,20 Earlier studies were largely based on the observation of patients treated with conventional chemotherapy regimens with idarubicin and cytarabine (ara-C). A new therapeutic regimen based on the combination of fludarabine and ara-C has been introduced in the past decade.…”

Thalidomide therapy induces response in relapsed mantle cell lymphoma

“…He was treated according to the current protocol at our institution, as reported elsewhere. 1 He received CHOP Â four cycles with only a partial response (PR), followed by highdose cytarabine-based chemotherapy (DHAP), and consolidation with an autologous stem cell transplant utilizing total body irradiation (TBI), melphalan, and cytarabine as the preparative regimen. A complete response (CR) was obtained.…”

High expression of the sister-chromatid separation regulator and proto-oncogene hSecurin occurs in a subset of myeloid leukaemias but is not implicated in the pathogenesis of aneuploidy

“…[2][3][4] Recent studies suggest that other numerical chromosome abnormalities may also represent adverse prognostic factors. [4][5][6] In chronic myeloid leukaemia (CML), progression from Philadelphia chromosome positive but otherwise karyotypically stable chronic phase (CP) to blast phase (BP) is commonly accompanied by the occurrence of various numerical chromosome aberrations. 7 Although there is considerable debate as to whether aneuploidy constitutes an initial step in carcinogenesis or is the consequence of earlier molecular events affecting chromosomal stability, it is generally regarded as an important factor in the pathogenesis of malignant diseases.…”