Somatic Mutations of<i>IDH1</i>and<i>IDH2</i>in the Leukemic Transformation of Myeloproliferative Neoplasms

Green, Anthony; Beer, Philip

doi:10.1056/nejmc0910063

Cited by 265 publications

(207 citation statements)

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“…Interestingly, Wnt3A was shown to preserve HSCs with an immature phenotype in vitro or to induce true stem cell characteristics in hematopoietic progenitors. 6,7 …”

Section: Wnt3a Nonredundantly Controls Hematopoietic Stem Cell Functimentioning

confidence: 99%

“…1 Very recently, a series of reports about this mutation in AML have been published in a cluster of manuscripts. [1][2][3][4][5][6][7] As IDH1 mutation brings prognostic information in glioma and possibly AML, 4,[8][9] identification of IDH1 R132 mutations will bring increasing clinical relevance. Moreover, the mutation seems quite stable and may serve as a marker for monitoring minimal residual disease.…”

mentioning

confidence: 99%

“…[1][2][3][4][5][6][7] Another upstream forward primer was used to generate a product as an internal control. Combination of these 7 forward primers and a common reverse primer ( Figure 1A) would generate a shorter mutant and a longer control product in any genomic DNA containing any type of R132 mutation, whereas only the longer product would be seen in samples without this mutation ( Figure 1B).…”

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confidence: 99%

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A single-tube, sensitive multiplex method for screening of isocitrate dehydrogenase 1 (IDH1) mutations

Chou

Huang

et al. 2010

Blood

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“…Interestingly, Wnt3A was shown to preserve HSCs with an immature phenotype in vitro or to induce true stem cell characteristics in hematopoietic progenitors. 6,7 …”

Section: Wnt3a Nonredundantly Controls Hematopoietic Stem Cell Functimentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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A single-tube, sensitive multiplex method for screening of isocitrate dehydrogenase 1 (IDH1) mutations

Chou

Huang

et al. 2010

Blood

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“…14,15 In a recent study, a significant clustering of TET2 mutations with post-MPN leukemia was reported, however, TET2 defects were not specific for the transformation. 16 A specific link to post-MPN transformation was provided by the identification of somatic mutations in the IDH1 and IDH2 genes, 17 the former proven to be strongly associated with normal karyotype. 18 To gain further insights into the genetic basis of the transition from chronic phase MPN to post-MPN leukemia, we analyzed transformed MPN patients for chromosomal aberrations using high-resolution microarray karyotyping and examined cytogenetic defects for specific association with post-MPN leukemia.…”

Section: Introductionmentioning

confidence: 99%

Deletions of the transcription factor Ikaros in myeloproliferative neoplasms

et al. 2010

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Transformation to acute leukemia is a major complication of myeloproliferative neoplasms (MPNs), however, the genetic changes leading to transformation remain largely unknown. We screened nine patients with post-MPN leukemia for chromosomal aberrations using microarray karyotyping. Deletions on the short arm of chromosome 7 (del7p) emerged as a recurrent defect. We mapped the common deleted region to the IKZF1 gene, which encodes the transcription factor Ikaros. We further examined the frequency of IKZF1 deletions in a total of 29 post-MPN leukemia and 526 MPN patients without transformation and observed a strong association of IKZF1 deletions with post-MPN leukemia in two independent cohorts. Patients with IKZF1 loss showed complex karyotypes, and del7p was a late event in the genetic evolution of the MPN clone. IKZF1 deletions were observed in both undifferentiated and differentiated myeloid cell types, indicating that IKZF1 loss does not cause differentiation arrest but rather renders progenitors susceptible to transformation, most likely through chromosomal instability. Induced Ikzf1 haploinsufficiency in primary murine progenitors resulted in elevated Stat5 phosphorylation and increased cytokine-dependent growth, suggesting that reduced expression of IKZF1 is sufficient to perturb growth regulation. Thus, IKZF1 loss is an important step in the leukemic transformation of a subpopulation of MPN patients.

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“…Monosomy 7 is an interesting lesion because it has a poor prognosis and targets many genes including IKZF1, CUX1, and EZH2 [26]. Second ary AML shares many defects with de novo AML such as IDH1/2, FLT3, DNMT3A, NPM1, and RUNX1 [26,[68][69][70][71][72][73][74][75]. This indicates that these genes may be involved in the overall leukomogenesis pathway but not specifically for transfor mation in MPNs.…”

Section: Clonal Evolution Of Mpn and Lesions Associated With Leukemicmentioning

confidence: 99%

Molecular basis and clonal evolution of myeloproliferative neoplasms

Cleary

Královics

2013

Clinical Chemistry and Laboratory Medicine (CCLM)

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Myeloproliferative neoplasms (MPNs) repre sent a group of diseases that affect the myeloid lineage, characterized by the presence of an excess of terminally differentiated myeloid cells. Defects causing clonal hematopoiesis are a key factor in the emergence of these diseases. Throughout the years, a number of causative defects have been identified, predominantly affecting cytokine signaling and gene expression regulation. This review aims to provide an update on the current status of the MPN field in relation to identification of molecular defects involved in the disease and its clonal evolution.

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Somatic Mutations ofIDH1andIDH2in the Leukemic Transformation of Myeloproliferative Neoplasms

Cited by 265 publications

References 5 publications

A single-tube, sensitive multiplex method for screening of isocitrate dehydrogenase 1 (IDH1) mutations

A single-tube, sensitive multiplex method for screening of isocitrate dehydrogenase 1 (IDH1) mutations

Deletions of the transcription factor Ikaros in myeloproliferative neoplasms

Molecular basis and clonal evolution of myeloproliferative neoplasms

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