A functional single-nucleotide polymorphism of the G-CSF receptor gene predisposes individuals to high-risk myelodysplastic syndrome

Wölfler, Albert; Erkeland, Stefan J.; Bodner, Claudia; Valkhof, Marijke; Renner, Wilfried; Leitner, Christina; Olipitz, Werner; Pfeilstöcker, Michael; Tinchon, Christoph; Emberger, Werner; Linkesch, Werner; Touw, Ivo P.; Sill, Heinz

doi:10.1182/blood-2004-06-2094

Cited by 46 publications

(31 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SNPs are the most common form of genetic variation between individuals, and recent reports have investigated the possibility that genetic polymorphisms in genes required for proliferation and differentiation may play a role in MDS development. Specifically, a GLU785Lys polymorphism in the G-CSF receptor was described and demonstrated functional alterations in growth factor responsiveness in high risk MDS patients suggesting a potential role in MDS pathophysiology [83]. It is likely that further investigations will reveal pathways impacted by these subtle changes in gene expression.…”

Section: Gain or Loss Of Gene Expression: Cytogenetic And Epigenetic mentioning

confidence: 99%

Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches

Warlick¹,

Smith²

2007

CCDT

View full text Add to dashboard Cite

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for progression, suggest that myelodysplastic syndromes encompass a multitude of disorders, likely involving numerous pathologic pathways. In fact, it is the effort to understand the underlying biology of these syndromes that has led to recent advances in treatment approaches, including the FDA approval of three new agents (5-azacitidine, decitabine, and lenalidomide) for the treatment of MDS. This review will present data supporting each of the current pathophysiologic pathways implicated in the development and progression of MDS; summarize the emerging clinical paradigms for treating patients with MDS; and offer insights into several novel approaches attempting to improve treatment options for future MDS patients.

show abstract

Section: Gain or Loss Of Gene Expression: Cytogenetic And Epigenetic mentioning

confidence: 99%

Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches

Warlick¹,

Smith²

2007

CCDT

View full text Add to dashboard Cite

show abstract

“…In contrast, other more common polymorphisms have now been identified in 'leukemia pathway' genes. [74][75][76] With regard to t-AML in particular, NRAS, KRAS, RUNX1 and TP53 are particularly good candidate t-AML susceptibility genes, since (a) mutations in these genes have been seen in 20-30% of t-AML cases, (b) mutations are more frequently seen in t-AML than in de novo AML and (c) inherited single nucleotide polymorphisms have been identified in these genes.…”

Section: Pharmacogenetic Risk Factors For Secondary Aml/mdsmentioning

confidence: 99%

Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients?

Hake

Graubert

Fenske

2006

Bone Marrow Transplant

View full text Add to dashboard Cite

Patients who undergo autologous stem cell transplantation (ASCT) for lymphoma have a significant risk of therapy-related acute myeloid leukemia and myelodysplasia (t-AML/MDS). Compared to that seen in other indications such as breast cancer, multiple myeloma or germ cell tumors, there is a substantially increased risk for t-AML/MDS following ASCT for lymphoma. This risk has largely been attributed to the extent of pre-transplant chemotherapy and radiation therapy. In many of the larger series to date, it has not been possible to directly implicate autologous transplantation itself as a risk factor for t-AML/MDS. Although pre-transplant therapy is certainly an important factor in the development of t-AML/MDS, specific components of the autologous transplantation procedure itself may also contribute to the risk of t-AML/MDS. Specifically, priming chemotherapy, total body irradiation, and the extensive cellular proliferation which occurs during engraftment may all play a role in the development of t-AML/MDS. Furthermore, there is an increasing body of evidence that certain inherited polymorphisms in genes governing drug metabolism, DNA repair and leukemogenesis may influence susceptibility to t-AML/MDS. In this paper, we review the evidence implicating the above risk factors for t-AML/MDS, present a potential mechanism for t-AML/ MDS and propose interventions to reduce the rate of t-AML/MDS in lymphoma patients.

show abstract

“…We speculated whether this SNP occurs more frequently in this new category, which has been underrepresented in the report by Wö lfler et al 1 We therefore analyzed a larger cohort of AML patients (n ¼ 445) including 346 patients with AML-MD treated within the AML-SHG 96 study. 3 Given the increased risk of high-risk MDS in patients carrying the polymorphism, we further investigated 80 MDS patients including a defined (n ¼ 21) population (refractory anemia: n ¼ 4, RA with excess blast (RAEB): n ¼ 10; RAEB in transformation: n ¼ 7) with a documented interval (median 7.1 months, range 0.2-73) from diagnosis to progression to AML from the Dü sseldorf MDS registry.…”

mentioning

confidence: 99%

“…Although our understanding of the pathophysiology of this disease has been greatly improved within recent years, the underlying factors relevant for the development of MDS have not been identified yet. Wö lfler et al 1 have recently shown that a single-nucleotide polymorphism (SNP) of the cytoplasmic domain of the granulocyte colony-stimulating factor (G-CSF) receptor at position 785 (G-CSF-R_Glu785Lys) predisposes for the development of high-risk MDS as defined by more than 5% marrow blasts. As a matter of fact, the SNP was detected in 7/72 (9.7%) of MDS patients, including five patients with secondary acute myeloid leukemia (AML) derived from MDS, compared to a frequency of 0.9% in normal controls.…”

mentioning

confidence: 99%

Association with the single-nucleotide polymorphism (Glu785Lys) of the granulocyte colony-stimulating factor receptor with myelodysplastic syndromes and acute myeloid leukemia with multlineage dysplasia

et al. 2006

View full text Add to dashboard Cite

A functional single-nucleotide polymorphism of the G-CSF receptor gene predisposes individuals to high-risk myelodysplastic syndrome

Cited by 46 publications

References 51 publications

Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches

Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches

Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients?

Association with the single-nucleotide polymorphism (Glu785Lys) of the granulocyte colony-stimulating factor receptor with myelodysplastic syndromes and acute myeloid leukemia with multlineage dysplasia

Contact Info

Product

Resources

About