Fluorescence in situ hybridization analysis of 110 hematopoietic disorders with chromosome 5 abnormalities: do de novo and therapy-related myelodysplastic syndrome–acute myeloid leukemia actually differ?

Lessard, Michel; Hélias, Catherine; Struski, Stéphanie; Perrusson, N; Uettwiller, Françoise; Mj, Mozziconacci; Lafage‐Pochitaloff, Marina; Dastugue, Nicole; Terré, Christine; Brizard, Françoise; Cornillet‐Lefèbvre, Pascale; Mugneret, Francine; Barin, Carole; Herry, Angèle; Luquet, Isabelle; Desangles, F; Michaux, Lucienne; Verellen‐Dumoulin, Christine; Perrot, Christine; Akker, Jacqueline van den; Lespinasse, James; Éclache, Virginie; Berger, Roland

doi:10.1016/j.cancergencyto.2007.01.013

Cited by 24 publications

(18 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12 Abnormalities of chromosome 5 are frequently found in patients with t-MDS, as well as those involving chromosome 7 or complex karyotypes. 43,44 Our data corroborated the poor prognosis conferred by isolated deletion 5q in t-MDS, which is in contrast with the favorable prognosis that the WHO classification bestows upon this chromosomal abnormality in patients diagnosed with de novo MDS. Finally, it will be interesting to compare the impact of cytogenetics in patients with MDS with a history of cancer that had not been treated with chemo or radiation therapy, versus the group studied here.…”

Section: Discussionsupporting

confidence: 79%

A Prognostic Model of Therapy-Related Myelodysplastic Syndrome for Predicting Survival and Transformation to Acute Myeloid Leukemia

Quintás‐Cardama

Daver

Kim

et al. 2014

Clinical Lymphoma Myeloma and Leukemia

View full text Add to dashboard Cite

Background We evaluated the characteristics of a cohort of patients with therapy-related myelodysplastic syndrome (t-MDS) to create a prognostic model. Patients and Methods We identified 281 patients with MDS that had received prior chemotherapy and/or radiotherapy for prior malignancy. Potential prognostic factors were determined by univariate and multivariate analysis. Results Multivariate Cox regression analysis identified 7 factors that independently predicted short survival in t-MDS: age ≥65 years (HR=1.63), ECOG performance status 2–4 (HR=1.86), poor cytogenetics (−7 and/or complex; HR=2.47), WHO MDS subtype (RARs or RAEB-1/2; HR=1.92), hemoglobin (<11g/dL; HR=2.24), platelets (<50×109/dL; HR=2.01), and transfusion dependency (HR=1.59). These risk factors were used to create a prognostic model that segregated patients into three groups with distinct median overall survival: good (0–2 risk factors; 34 months), intermediate (3–4 risk factors; 12 months) and poor (5–7 risk factors; 5 months) (p<0.001) and 1-year leukemia free survival (96%, 84%, and 72%, respectively, p=0.003). This model also identified distinct survival groups according to t-MDS therapy. Conclusion In summary, we devised a prognostic model specifically for patients with t-MDS that predicts overall survival and leukemia-free survival. This model may facilitate the development of risk-adapted therapeutic strategies.

show abstract

Section: Discussionsupporting

confidence: 79%

A Prognostic Model of Therapy-Related Myelodysplastic Syndrome for Predicting Survival and Transformation to Acute Myeloid Leukemia

Quintás‐Cardama

Daver

Kim

et al. 2014

Clinical Lymphoma Myeloma and Leukemia

View full text Add to dashboard Cite

show abstract

“…It identified two molecular sub-groups, here named NPM1 +/− and NPM1 +/+, since it was present in 38/84 (45%) cases with complex karyotypes and 5q-. Interestingly Lessard et al [18] demonstrated loss of the 5q35 chromosome band in 30% of de novo and therapy related AML. NPM1 loss may have occurred as an early step in MDS/AML as it remained stably mono-allelic in 4 NPM1+/− patients and did not develop in 6 NPM1+/+ over a median of 9 months follow-up (range: 2–156 months) ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

NPM1 Deletion Is Associated with Gross Chromosomal Rearrangements in Leukemia

et al. 2010

View full text Add to dashboard Cite

Background NPM1 gene at chromosome 5q35 is involved in recurrent translocations in leukemia and lymphoma. It also undergoes mutations in 60% of adult acute myeloid leukemia (AML) cases with normal karyotype. The incidence and significance of NPM1 deletion in human leukemia have not been elucidated.Methodology and Principal FindingsBone marrow samples from 145 patients with myelodysplastic syndromes (MDS) and AML were included in this study. Cytogenetically 43 cases had isolated 5q-, 84 cases had 5q- plus other changes and 18 cases had complex karyotype without 5q deletion. FISH and direct sequencing investigated the NPM1 gene. NPM1 deletion was an uncommon event in the “5q- syndrome” but occurred in over 40% of cases with high risk MDS/AML with complex karyotypes and 5q loss. It originated from large 5q chromosome deletions. Simultaneous exon 12 mutations were never found. NPM1 gene status was related to the pattern of complex cytogenetic aberrations. NPM1 haploinsufficiency was significantly associated with monosomies (p<0.001) and gross chromosomal rearrangements, i.e., markers, rings, and double minutes (p<0.001), while NPM1 disomy was associated with structural changes (p = 0.013). Interestingly, in complex karyotypes with 5q- TP53 deletion and/or mutations are not specifically associated with NPM1 deletion.Conclusions and Significance NPM1/5q35 deletion is a consistent event in MDS/AML with a 5q-/-5 in complex karyotypes. NPM1 deletion and NPM1 exon 12 mutations appear to be mutually exclusive and are associated with two distinct cytogenetic subsets of MDS and AML.

show abstract

“…Various types of whole-arm translocation have been reported to be recurrent anomalies. Of these, der(5;17)(p10;q10) is reported to be a recurrent but rare chromosomal aberration that is associated with hematological malignancies [2,3,4,5,6,7,8,9,10,11,12,13]. We identified 3 patients with myeloid malignancies that harbored the der(5;17)(p10;q10) translocation.…”

Section: Introductionmentioning

confidence: 89%

“…Among such cases, the loss of 17p is reported to be the most common form of short-arm loss and often occurs as part of complex karyotypes that are suggestive of disease progression [9]. To the best of our knowledge, only about 20 cases of hematological malignancies involving the der(5;17)(p10;q10) whole-arm translocation, which results in the loss of 5q and 17p, together with complex chromosomal abnormalities have been reported in the literature [2,3,4,5,6,7,8,9,10,11,12,13]. As for the role of whole-arm translocations in leukemogenesis, it has been suggested that the genomic imbalances caused by unbalanced whole-arm translocations are likely to have functional consequences.…”

Section: Discussionmentioning

confidence: 99%

der(5;17)(p10;q10) Is a Recurrent But Rare Whole-Arm Translocation in Patients with Hematological Neoplasms: A Report of Three Cases

Manabe¹,

Okita²,

Tarakuwa³

et al. 2014

Acta Haematol

View full text Add to dashboard Cite

We report the cases of 3 patients with hematological malignancies and complex karyotypes involving der(5;17)(p10;q10), which results in the loss of 5q and 17p. Although deletions of 5q and 17p are recurrent abnormalities in hematological disease, only about 20 cases harboring der(5;17)(p10;q10) have been reported. We address the tumorigenesis and morphological characteristics of hematological malignancies involving der(5;17)(p10;q10), along with a review of the literature.

show abstract

Fluorescence in situ hybridization analysis of 110 hematopoietic disorders with chromosome 5 abnormalities: do de novo and therapy-related myelodysplastic syndrome–acute myeloid leukemia actually differ?

Cited by 24 publications

References 24 publications

A Prognostic Model of Therapy-Related Myelodysplastic Syndrome for Predicting Survival and Transformation to Acute Myeloid Leukemia

A Prognostic Model of Therapy-Related Myelodysplastic Syndrome for Predicting Survival and Transformation to Acute Myeloid Leukemia

NPM1 Deletion Is Associated with Gross Chromosomal Rearrangements in Leukemia

der(5;17)(p10;q10) Is a Recurrent But Rare Whole-Arm Translocation in Patients with Hematological Neoplasms: A Report of Three Cases

Contact Info

Product

Resources

About