Original articleAdditional cytogenetic changes and previous genotoxic exposure predict unfavorable prognosis in myelodysplastic syndromes and acute myeloid leukemia with der(1;7)(q10;p10)
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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Cited by (17)
Does MDS with der(1;7)(q10;p10) constitute a distinct risk group? A retrospective single institutional analysis of clinical/pathologic features compared to -7/del(7q) MDS
2009, Cancer Genetics and CytogeneticsCitation Excerpt :In MDS, for example, most patients present with multilineage dysplasia in the bone marrow, pancytopenia in the peripheral blood, and a poor prognosis with a high progression rate to AML. In addition, der(1;7) in MDS is associated with a history of therapeutic or environmental exposure to toxic substances in 40–50% of patients and occasionally with eosinophilia [2–4]. The der(1;7) is currently considered a “karyotypic variant” of the del(7q)/–7 subgroup and has been assigned a poor risk karyotype score in the International Prognostic Scoring System or IPSS, a clinical scoring system that estimates overall survival (OS) and risk of AML transformation [5].
Acute erythroleukemia with der(1;7)(q10;p10) as a sole acquired abnormality after treatment with azathioprine
2008, Cancer Genetics and CytogeneticsA der(1;15)(q10;q10) is a rare nonrandom whole-arm translocation in patients with acute lymphoblastic leukemia
2007, Cancer Genetics and CytogeneticsCitation Excerpt :Whole-arm translocations (WATs) in hematological malignancies are not common chromosomal aberrations [7]. However, certain abnormalities such as der(1;7)(q10;p10) are frequently found in myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), and myeloproliferative disorders (MPD) as sole anomalies, and clinical implications have been reported [8]. Indeed, ∼11 different unbalanced WATs, including der(1;15)(q10;q10), have been reported as recurrent sole anomalies in hematological malignancies [2,7].
Translocation (4;11)(p12;q23) with rearrangement of FRYL and MLL in therapy-related acute myeloid leukemia
2007, Cancer Genetics and CytogeneticsCitation Excerpt :Our patient, however, had not received a topoisomerase II inhibitor, but rather only fludarabine, rituximab and radiation therapy. Several previous patients with therapy-related myelodysplastic syndrome (t-MDS) and t-AML after fludarabine alone have been reported, and all had cytogenetic abnormalities, which included complex karyotypes and chromosome 5 and 7 abnormalities, but not 11q23 translocations [10–12]. The relationship between the t(4;11)(p12;q23) in our patient and her prior cytotoxic therapy is unclear.
Recurrent unbalanced whole-arm t(1;10)(q10;p10) in myelodysplastic syndrome: a case report and literature review
2007, Cancer Genetics and CytogeneticsCitation Excerpt :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].
Risk factor analysis in myelodysplastic syndrome patients with del(20q): prognosis revisited
2006, Cancer Genetics and CytogeneticsCitation Excerpt :The incidence of sole del(20q) anomaly in therapy-related MDS and AML is less common [28], however, therapy-related MDS with del(20q) as one among several cytogenetic changes may exist: two patients with der(1;7)(q10;p10) and two with other cytogenetic abnormalities were found to have prior exposure of genotoxic agents in this study. The additional cytogenetic changes and prior genotoxic exposure was found to be linked to unfavorable prognostic predictors in MDS and AML patients with der(1;7)(q10;p10) [18]. Possibilities such as the cumulative probability of mutational events or genetic instability or age-related predisposition to secondary malignancy need to be explored regarding the genesis of del(20q).