Original article
Additional cytogenetic changes and previous genotoxic exposure predict unfavorable prognosis in myelodysplastic syndromes and acute myeloid leukemia with der(1;7)(q10;p10)

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Abstract

We analyzed 23 patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) showing a der(1;7)(q10;p10) [hereafter der(1;7)] to identify the exact predictive factor of this cytogenetic change. Eight (34.8%) patients, including six with MDS and two with AML patients, had a previous history of genotoxic exposure, especially radiation and/or antimetabolites. Patients with der(1;7) consisted of three groups: one third of patients had a previous history of genotoxic agents, one third had additional cytogenetic changes at the time of MDS/AML diagnosis without previous exposure history, and the remaining one third had neither a previous exposure history nor additional cytogenetic changes. The current study demonstrated that the poor outcome of MDS/AML with der(1;7) is caused by the high frequency of associated risk factors (i.e., previous history of genotoxic exposure, the presence of additional cytogenetic changes, or both). Identification of prognostic disadvantage might be required for applying the appropriate strategy in managing MDS/AML patients with rare der(1;7) abnormality.

Introduction

Chromosome 7 abnormalities (–7/7q–) are the most common chromosome changes in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), especially in secondary MDS and AML [1], [2], [3], [4]. Nonetheless, the unbalanced translocation of chromosomes 1 and 7, der(1;7)(q10;p10) [hereafter der(1;7)], which results in trisomy 1q and monosomy 7p, is relatively rare in MDS and/or AML with cytogenetic abnormalities [5], [6], [7]. This abnormality was first reported by Geraedts et al. [8], and other investigators also confirmed this as a nonrandom abnormality in myeloid disorders, sometimes found to be therapy related [9], [10], [11]. The abnormality appears to be associated with dysplastic features in the marrow and poor prognosis [11], [12], [13], [14], [15]: the International Prognostic Scoring System (IPSS) for MDS adopted an abnormality of chromosome 7, including der(1;7), as one of the poor cytogenetic indicators [16]. Although some MDS cases with der(1;7) were actually therapy related and had unfavorable prognoses, the exact clinico-hematologic features are not fully understood because the number of patients with der(1;7) is still small. In this report, we analyzed 23 MDS/AML patients with der(1;7) from a single institution to attempt to evaluate the prognostic impact of this abnormality.

Section snippets

Patients

From 1988 to 2004, a total of 27 patients with der(1;7) were detected in chromosome examinations in our hospital. Among them, four patients with chronic myeloproliferative disorders with der(1;7) were excluded from this study and will be discussed elsewhere [17]. A total of 23 cases, including 19 MDS patients (3.7% = 19/515 total MDS patients) and 4 AML patients (1.6% = 4/244 total AML patients), were eligible and all gave their informed consent to enroll in the study. Clinical data, past

Cytogenetics results

Ten of 23 patients (43.5%) had a sole der(1;7) abnormality, including 8 RA, 1 RA with excess blasts (RAEB), and 1 AML patients (Table 1): 2 patients (unique patient numbers 110 and 113) showed an unrelated clone with a missing Y chromosome, thus they were included in the group of sole der(1;7) rather than in the additional changes group. The other 13 cases, including 8 RA, 2 RAEB, and 3 AML patients, had other abnormalities in addition to der(1;7): 9 cases showed a single additional

Discussion

The unbalanced translocation between chromosomes 1 and 7, der(1;7)(q10;p10), is a nonrandom translocation in hematologic diseases. Since the initial report by Geraedts et al. [8], more than 100 cases have been reported [19]. Though the exact mechanism of the formation of this translocation is still unclear, this abnormality is frequently found in myeloid disorders and is associated with genotoxic exposure and poor prognosis [11], [15]. In the series, we found that 34.8% of patients (8/23) with

Acknowledgments

The authors are indebted to Prof. J. Patrick Barron of the International Medical Communications Center of Tokyo Medical University for his review of this manuscript. This work has been supported in part by a Grant-in-Aid for Intractable Hematopoietic Diseases from the Ministry of Health, Welfare, and Labor, Japan, the High-Tech Research Center Project from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), and by the University-Industry Joint Research Project from MEXT.

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    Recurring centromeric translocation in neoplastic cells is well known, and certain anomalies are clustered in subtypes of human hematologic neoplasia. For example, der(1;7)(q10;p10) is frequently found in MDS/AML as a sole abnormality and its clinical implication has been reported [3]. A review of the literature demonstrated that der(1;16)(q10;p10) or der(1;19)(q10;p10) were clustered in patients with multiple myeloma as additional changes (Table 1) [4].

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