<scp>TP</scp>53 mutations and MDM2SNP309 identify subgroups of <scp>AML</scp> patients with impaired outcome

Falk, Ingrid Jakobsen; Willander, Kerstin; Chaireti, Roza; Lund, Johan; Nahi, Hareth; Hermanson, Monica; Gréen, Henrik; Lotfi, Kourosh; Söderkvist, Peter

doi:10.1111/ejh.12438

Cited by 18 publications

(17 citation statements)

References 22 publications

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“…In AML patients without FLT3-ITD, variant allele of rs10883841 in 5-NT was associated with shorter survival [26]. In addition, polymorphisms of other genes were also identified to be responsible for the prognosis of AML patients [53,54]. Therefore, more parameters need to be included for better prognostic stratification.…”

Section: Discussionmentioning

confidence: 99%

SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study

Wan

Zhu

Chen

et al. 2014

J Exp Clin Cancer Res

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Section: Discussionmentioning

confidence: 99%

SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study

Wan

Zhu

Chen

et al. 2014

J Exp Clin Cancer Res

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“…Selected examples include FLT3-ITD and mutations affecting p53. 5,40 INPP4B overexpression has previously been linked to poor OS as part of a leukemic stem cell gene expression signature in AML. 41 In our current study, we substantially extend these observations by showing that high INPP4B, defined as protein positivity in at least 50% of AML blasts, delineates a high-risk patient population characterized by reduced response to induction chemotherapy, earlier leukemic relapse, and poorer OS outcome.…”

Section: Inpp4b Overexpression Confers Resistance To Chemotherapy In mentioning

confidence: 99%

Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML

Rijal

Fleming

Cummings

et al. 2015

Blood

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Phosphoinositide signaling regulates diverse cellular functions. Phosphoinositide-3 kinase (PI3K) generates PtdIns(3,4,5)P 3 and PtdIns(3,4)P 2 , leading to the activation of proliferative and anti-apoptotic signaling pathways. Termination of phosphoinositide signaling requires hydrolysis of inositol ring phosphate groups through the actions of PtdIns(3,4,5)P 3 3-phosphatase (PTEN), PtdIns(3,4,5)P 3 5-phosphatases (eg, SHIP), and PtdIns(3,4)P 2 4-phosphatases (eg, INPP4B). The biological relevance of most of these phosphoinositide phosphatases in acute myeloid leukemia (AML) remains poorly understood. Mass spectrometry-based gene expression profiling of 3-, 4-and 5-phosphatases in human AML revealed significant overexpression of INPP4B. Analysis of an expanded panel of 205 AML cases at diagnosis revealed INPP4B overexpression in association with reduced responses to chemotherapy, early relapse, and poor overall survival, independent of other risk factors. Ectopic overexpression of INPP4B conferred leukemic resistance to cytosine arabinoside (ara-C), daunorubicin, and etoposide. Expression of a phosphatase inert variant (INPP4B C842A) failed to abrogate resistance of AML cells to chemotherapy in vitro or in vivo. In contrast, targeted suppression of endogenously overexpressed INPP4B by RNA interference sensitized AML cell lines and primary AML to chemotherapy. These findings demonstrate a previously unsuspected and clinically relevant role for INPP4B gain of function as a mediator of chemoresistance and poor survival outcome in AML independent of its phosphoinositide phosphatase function. (Blood. 2015;125(18):2815-2824

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“…The MDM-2 (MIM#164785) gene encodes a 90-kDa protein that binds specifically to the p53 tumor suppressor and directly inhibiting the transcriptional activity of P53 (Ard et al, 2002;Dimitriadi et al, 2008;Falk et al, 2015). Moreover, MDM2 functions as an E3 ubiquitin ligase is responsible for the ubiquitination and proteolytic degradation of p53 (Gohari et al, 2016;Neamatzadeh et al, 2015).…”

Section: Association Of Mouse Double Minute 2 -309t>g Polymorphism Wimentioning

confidence: 99%

Association of Mouse Double Minute 2 -309T>G Polymorphism with Acute Myeloid Leukemia in an Iranian Population: A Case- Control Study

Soleymannejad

Sheikhha

Neámatzadeh

2019

Asian Pac J Cancer Prev

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Background: Genetic factors play a substantial role in acute myeloid leukemia (AML) etiology. Overexpression of the mouse double minute 2 (MDM2) gene has been explored in many tumors. However, the role of MDM2-309T>G (rs2279744) polymorphism in AML remains unclear. We have performed this study to examine the association of MDM2-309T>G with AML in an Iranian population. Methods: We have examined the association of N MDM2-309T>G polymorphism in 73 cases diagnosed with AML and 80 healthy controls by tetra-primer amplification refractory mutation system (ARMS) PCR assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on the risk genotypes and alleles. Results: The TT, GG and GG genotypes of MDM2-309T>G polymorphism in patients were 32.9%, 23.2% and 43.9%, while in controls were 86.2%, 7.5% and 6.3%, respectively. Moreover, Frequency of mutant allele (G) was 55.6% in cases with AML and 10.0% in controls. The mutant homozygote genotype (GG) was associated with an increased susceptibility to AML (OR 1.471; 95% CI: 1.062-1.844; p=0.004). Conclusion: Our results showed that the MDM2-309T>G polymorphism was significantly associated with increased risk of AML in the Iranian population. Thus, the MDM2-309T>G polymorphism might be useful genetic susceptibility factors in the pathogenesis of AML.

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TP53 mutations and MDM2^SNP309 identify subgroups of AML patients with impaired outcome

Abstract: Background: TP53 is commonly mutated in several cancers and confers treatment resistance

Cited by 18 publications

References 22 publications

SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study

SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study

Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML

Association of Mouse Double Minute 2 -309T>G Polymorphism with Acute Myeloid Leukemia in an Iranian Population: A Case- Control Study

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TP53 mutations and MDM2SNP309 identify subgroups of AML patients with impaired outcome

Abstract: Background: TP53 is commonly mutated in several cancers and confers treatment resistance

Cited by 18 publications

References 22 publications

SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study

SLC29A1 single nucleotide polymorphisms as independent prognostic predictors for survival of patients with acute myeloid leukemia: an in vitro study

Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML

Association of Mouse Double Minute 2 -309T>G Polymorphism with Acute Myeloid Leukemia in an Iranian Population: A Case- Control Study

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TP53 mutations and MDM2^SNP309 identify subgroups of AML patients with impaired outcome