Sole abnormalities of chromosome 7 in myeloid malignancies: Spectrum, histopathologic correlates, and prognostic implications

Hussain, Fareeda Taher Nazer; Nguyen, Edward; Raza, Sania S.; Knudson, Ryan A.; Pardanani, Animesh; Hanson, Curtis A.; Dyke, Daniel Van; Tefferi, Ayalew

doi:10.1002/ajh.23230

Cited by 29 publications

(34 citation statements)

References 14 publications

(23 reference statements)

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“…Consistent with previous reports (1–5), the outcomes of sole -7 AML patients were very poor, with only 42% of patients achieving a CR. The median DFS was 8.4 months and the median OS was 9.2 months (Table 2).…”

Section: Resultssupporting

confidence: 91%

“…The adverse prognostic impact of -7, both in combination with other chromosomal aberrations and as a sole abnormality, has been well known for decades. Patients with -7 are characterized by low initial complete remission (CR) rates, short remissions, and inferior survival compared with those of patients in most other cytogenetic groups (1–5). The elucidation of the underlying biology and identification of candidate genes responsible for the adverse clinical outcome of -7 AML have been the focus of numerous studies (6–14), but a comprehensive study using next-generation sequencing of a cohort of sole -7 AML patients without (possibly confounding) other cytogenetic abnormalities has not been reported to date.…”

Section: Introductionmentioning

confidence: 99%

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Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality

et al. 2017

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Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML) which may give insights into the basis for its poor prognosis have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and microRNA expression profiles were also determined using paired RNA and small RNA sequencing data. Notably, gene mutations were detected in all the major AML-associated functional groups, which include activated signaling, chromatin remodeling, cohesin complex, methylation, NPM1, spliceosome, transcription factors and tumor suppressors. Gene mutations in the activated signaling and chromatin remodeling groups were relatively more frequent in patients <60 years of age, who also had more mutations in the methylation and spliceosome groups compared to patients {greater than or equal to} 60 years of age. Novel recurrent mutational events in AML were identified in the SMARCA2 gene. In patients {greater than or equal to} 60 years of age, the presence of spliceosome mutations associated with a lower complete remission rate (p=0.03). RNA sequencing revealed distinct gene and microRNA expression patterns between the sole -7 and non-7 AML cases, with reduced expression as expected of many genes and microRNAs mapped to chromosome 7, and overexpression of ID1, MECOM, and PTPRM, among others. Overall, our findings illuminate a number of molecular features of the underlying aggressive pathobiology in -7 AML patients.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality

et al. 2017

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“…However, once again this datum was not confirmed by multivariate analysis. Thus, our data partially research article agree with a recent study that analyzed the prognostic implications of sole chromosome seven abnormalities in myeloid malignancies [38]. That study reported no significant difference in OS and LFS comparisons, adjusted for the presence of either excess blasts or multilineage dysplasia among patients with der(1;7)(p10;p10), del(7q), and 27.…”

Section: Discussionsupporting

confidence: 92%

Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

et al. 2013

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This study evaluated whether the NCCSS truly improves the prognostic stratification of 630 consecutive de novo MDS patients and established which cytogenetic grouping [NCCSS or International Prognostic Scoring System (IPSS)], when combined with the WHO classification, best predicted the clinical outcome of myelodysplastic syndromes (MDS). The frequency of chromosomal defects was 53.8%. Clinical parameters, including number of cytopenias, WHO classification, IPSS cytogenetic categories and scores, NCCSS were all relevant for overall survival (OS) and leukemia-free survival (LFS) and were included in six distinct multivariate models compared by the Akaike Information Criterion (AIC). The most effective model to predict OS included the number of cytopenias, the WHO classification and the NCCSS, whereas the model including the number of cytopenias, blast cell percentage and the NCCSS and the model including the number of cytopenias the WHO classification and the NCCSS were almost equally effective to predict LFS. In conclusion, the NCCS (i) improves the prognostic stratification of the good and poor IPSS cytogenetic categories by introducing the very good and the very poor categories; (ii) is still incomplete in establishing the prognostic relevance of rare/double defects, (ii) applied to patients who receive supportive treatment only identifies five different prognostic subgroups, but applied to patients treated with specific therapies reveals only a trend toward a significantly different OS and LFS when patients of the poor and intermediate cytogenetic categories are compared, (iii) combined with the WHO classification is much more effective than the IPSS in predicting MDS clinical outcome. Am. J. Hematol. 88:120-129,

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“…In addition, two copies of apparently normal chromosomes 1 and a single copy of intact chromosome 7 are present (Figure A). Regarding the prognostic impact of der(1;7) there are conflicting data showing dismal, intermediate, and favorable prognosis of der(1;7), precluding reliable therapy allocation, in particular with regard to proceeding to allogeneic hematopoietic stem cell transplantation (HSCT) or not. Allogeneic HSCT is increasingly used as curative treatment option in MDS .…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes

Ganster

Müller‐Thomas

Haferlach

et al. 2019

Genes Chromosomes & Cancer

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The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled “any other single” and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data. The aim of our international collaborative was to clarify the “real” prognostic impact of der(1;7) on a homogenous and well‐documented data base. We performed detailed analysis of 63 MDS patients with isolated der(1;7) constituting the largest cohort hitherto reported. Furthermore, clinical data are compared with those of patients with isolated del(7q) and isolated monosomy 7. Median overall survival (OS) of patients with der(1;7) is 26 months (hazard ratio (HR) 0.91 for del(7q) vs der(1;7) and 2.53 for monosomy 7 vs der(1;7)). The der(1;7) is associated with profound thrombocytopenia most probably causing the reduced OS which is in striking contrast to the low risk for AML transformation (HR 3.89 for del(7q) vs der(1;7) and 5.88 for monosomy 7 vs der(1;7)). Molecular karyotyping indicates that der(1;7) is generated in a single step during mitosis and that a chromosomal imbalance rather than a single disrupted gene accounts for malignancy. Thus, the current cytogenetic scoring system assigning isolated der(1;7) to the intermediate risk group is now confirmed by a sufficient data set.

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Sole abnormalities of chromosome 7 in myeloid malignancies: Spectrum, histopathologic correlates, and prognostic implications

Cited by 29 publications

References 14 publications

Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality

Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality

Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes

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