Recurrent genetic defects on chromosome 7q in myeloid neoplasms

Hosono, Naoko; Makishima, Hideki; Jerez, Andrés; Yoshida, Kenichi; Przychodzen, Bartlomiej; McMahon, Sandra; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Sanada, Masashi; Gómez-Seguí, Inés; Verma, Amit; McDevitt, Michael A.; Sekeres, Mikkael A.; Ogawa, Seishi; Maciejewski, Jaroslaw P.

doi:10.1038/leu.2014.25

Cited by 42 publications

(53 citation statements)

References 34 publications

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“…Del(7q) was persistently detected in 15 patients (including 13 patients who were ultimately diagnosed with therapy-related myeloid neoplasms), and became undetectable in 12 patients (11 who were not diagnosed with therapy-related myeloid neoplasms). Two patients (cases 15 and 17) showed clonal evolution with additional chromosomal abnormalities after 8 and 22 months respectively, and 2 patients (cases 18 and 36) had new unrelated clones that emerged after del(7q) disappeared, specifically case 18 showed 45,XY,der(6;7) (p10;q10) [4]/46,XY,add(11)(p15) [3]/46,XY [13], and case 36 showed 46,XY,del(11)(q22q23) [16]/46,XY [4].…”

Section: Follow-up and Outcomesmentioning

confidence: 99%

“…[1][2][3] Del(7q)/ − 7 occurs in~8% of de novo acute myeloid leukemia and~10% of de novo myelodysplastic syndromes. 1,4 Del(7q) has been classified as the intermediate-II risk group in de novo acute myeloid leukemia 5 and the intermediate risk group in de novo myelodysplastic syndromes, respectively. 6 Therapy-related myeloid neoplasm is a late complication of cytotoxic therapies for primary malignant and non-malignant diseases.…”

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confidence: 99%

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Newly emerged isolated Del(7q) in patients with prior cytotoxic therapies may not always be associated with therapy-related myeloid neoplasms

et al. 2016

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Deletion 7q is a common chromosomal abnormality in myeloid neoplasms. Detection of del(7q) in patients following cytotoxic therapies is highly suggestive of an emerging therapy-related myeloid neoplasm. In this study, we describe 39 patients who acquired del(7q) as a sole abnormality in their bone marrow following cytotoxic therapies for malignant neoplasms. The median interval from cytotoxic therapies to detection of del(7q) was 40 months (range, 4-190 months). Twenty-eight patients showed an interstitial and 11 showed a terminal 7q deletion. Fifteen patients (38%) had del(7q) as a large clone and 24 (62%) as a small clone. With a median followup of 21 months (range, 1-135 months), 18 (46%) patients developed therapy-related myeloid neoplasms, including all 15 patients with a large del(7q) clone and 3/24 (12.5%) with a small clone. Of the remaining 21 patients with a small del(7q) clone, 16 showed no evidence of therapy-related myeloid neoplasms and 5 had an inconclusive pathological diagnosis. We conclude that isolated del(7q) emerging in patients after cytotoxic therapy may not always be associated with therapy-related myeloid neoplasms in about half of patients. The clone size of del(7q) is critical; a large clone is almost always associated with therapy-related myeloid neoplasms, whereas a small clone can be a clinically indolent or transient finding. Abnormalities of chromosome 7, either monosomy (−7) or deletion of the long arm (del(7q)), are the most common cytogenetic abnormalities detected in acute myeloid leukemia and myelodysplastic syndromes. 1-3 Del(7q)/ − 7 occurs in~8% of de novo acute myeloid leukemia and~10% of de novo myelodysplastic syndromes. 1,4 Del(7q) has been classified as the intermediate-II risk group in de novo acute myeloid leukemia 5 and the intermediate risk group in de novo myelodysplastic syndromes, respectively. 6 Therapy-related myeloid neoplasm is a late complication of cytotoxic therapies for primary malignant and non-malignant diseases. Cytogenetic abnormalities can be detected in more than 90% of patients with therapy-related myeloid neoplasms, and more than half of these patients have a complex karyotype. 7 Del(7q)/ − 7 presents in~50% of patients with therapy-related myeloid neoplasms and are often associated with prior exposure to alkylating agents or ionizing radiation. 1,[8][9][10][11][12][13] Any newly emerged cytogenetic abnormalities in patients with a prior history of cytotoxic therapies often raises the concern of development of therapy-related myeloid neoplasms, especially when the abnormalities include del(7q)/ − 7.In our practice, we have observed that some patients develop isolated del(7q) in their bone marrow following cytotoxic therapies, yet never develop therapy-related myeloid neoplasms with close follow-up. In order to better understand the

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Section: Follow-up and Outcomesmentioning

confidence: 99%

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confidence: 99%

Newly emerged isolated Del(7q) in patients with prior cytotoxic therapies may not always be associated with therapy-related myeloid neoplasms

et al. 2016

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“…[12][13][14][15][16][17][18][19][20][21][22] In an early study of ours, we identified disease-specific dysregulated genes and pathways using GeneChip analysis of bulk CD34 1 hematopoietic stem (HSCs) and progenitor cells (HSPCs) from patients with MDS with monosomy 7. 20 However, the absence of specific cell-membrane markers to separate cytogenetically normal and abnormal cells hindered further analysis of dysregulated molecular mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Single-cell RNA-seq reveals a distinct transcriptome signature of aneuploid hematopoietic cells

Zhao

Gao

et al. 2017

Blood

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“…In our case, monosomy 7 was not found by MC, but detected by the SNP-A-based karyotyping. Recent whole-exon sequencing (WES) and expression analysis of both cases with deletions and those with an apparently normal diploid chromosome 7 have demonstrated the various associations of the loss of heterogeneity (LOH) of 7q with or without concomitant mutations in genes located in the 7q region with patient prognosis (Hosono et al 2014). The SNP-A analysis achieves superb resolution and can detect copy number-neutral AOH or LOH, thereby overcoming shortcomings such as fewer mitoses, myelofibrosis in MC or fluorescence in situ hybridization (FISH).…”

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confidence: 99%

Diabetes Insipidus as an Initial Presentation of Myelodysplastic Syndrome: Diagnosis with Single-Nucleotide Polymorphism Array-Based Karyotyping

Sun

Wang

Zhong

et al. 2016

Tohoku J. Exp. Med.

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Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic diseases characterized by cytopenia, dysplasia and increased risk of development to acute myeloid leukemia (AML). Unfavorable cytogenetic changes such as complex karyotypes or chromosome 7 anomalies are predictive of the progression to AML and poor prognosis. Central diabetes insipidus (CDI) is the result of a deficiency of arginine vasopressin, and its major causes are idiopathic, primary or secondary tumors, neurosurgery and trauma. Importantly, CDI is a rare complication of MDS. To date, only 5 cases of MDS co-occurring with CDI have been reported; 3 of 5 had cytogenetic abnormalities uncovered by metaphase cytogenetics and 3 of 5 evolved to AML. Here, we describe a 74-year-old woman who presented with CDI as her initial symptom of MDS and eventually progressed to AML. The metaphase cytogenetics, combined with the single-nucleotide polymorphism array (SNP-A)-based karyotyping, with superiority in resolution and detecting copy number variation, revealed a complex karyotype that included monosomy of chromosome 7, deletion of 20q, and absence of heterogeneity (AOH) in more than one chromosome. To the best of our knowledge, this is the first case report of MDS co-occurring with CDI with numerous cytogenetic abnormalities revealed by the SNP-A-based karyotyping. Our case supports that the cytogenetic abnormalities may be associated with the clinical features and the prognosis of MDS co-occurring with CDI. The SNP-A-based karyotyping is helpful in revealing more subtle cytogenetic abnormalities and unveiling their roles in the pathogenesis of MDS.

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Recurrent genetic defects on chromosome 7q in myeloid neoplasms

Abstract: Background: Deletion of chromosome 5q (del(5q)) is the most common

Cited by 42 publications

References 34 publications

Newly emerged isolated Del(7q) in patients with prior cytotoxic therapies may not always be associated with therapy-related myeloid neoplasms

Newly emerged isolated Del(7q) in patients with prior cytotoxic therapies may not always be associated with therapy-related myeloid neoplasms

Single-cell RNA-seq reveals a distinct transcriptome signature of aneuploid hematopoietic cells

Diabetes Insipidus as an Initial Presentation of Myelodysplastic Syndrome: Diagnosis with Single-Nucleotide Polymorphism Array-Based Karyotyping

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