Analyses of TET2 mutations in post-myeloproliferative neoplasm acute myeloid leukemias

Couronné, Lucile; Lippert, Éric; Andrieux, Joris; Kosmider, Olivier; Radford‐Weiss, Isabelle; Penther, Dominique; Dastugue, Nicole; Mugneret, Francine; Lafage, Marina; Gachard, Nathalie; Nadal, Nathalie; Bernard, Olivier; Nguyen‐Khac, Florence

doi:10.1038/leu.2009.169

Cited by 44 publications

(31 citation statements)

References 8 publications

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“…[3][4][5][6][7][8][9][10][11] TET2 is mutated in 13% of the MPN cases, with the highest frequency occurring in patients with primary myelofibrosis (PMF) and polycythemia vera (PV; 17% and 16%, respectively) and lowest in patients with essential thrombocythemia (ET; 5%). 3 The mutations in TET2 do not cluster in a particular region and show a very diverse pattern of frame shift, nonsense, and missense mutations.…”

Section: Introductionmentioning

confidence: 99%

Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms

Schaub

Looser

et al. 2010

Blood

162

127

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Somatic mutations in TET2 occur in patients with myeloproliferative neoplasms and other hematologic malignancies. It has been suggested that TET2 is a tumor suppressor gene and mutations in TET2 precede the acquisition of JAK2-V617F. To examine the order of events, we performed colony assays and genotyped TET2 and JAK2 in individual colonies. In 4 of 8 myeloproliferative neoplasm patients, we found that some colonies with mutated TET2 carried wild-type JAK2, whereas others were JAK2-V617F positive, indicating that TET2 occurred before JAK2-V617F. One of these patients carried a germline TET2 mutation. However, in 2 other patients, we obtained data compatible with the opposite order of events, with JAK2 exon 12 mutation preceding TET2 mutation in one case. Finally, in 2 of 8 patients, the TET2 and JAK2-V617F mutations defined 2 separate clones. The lack of a strict temporal order of occurrence makes it unlikely that mutations in TET2 represent a predisposing event for acquiring mutations in JAK2.

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Section: Introductionmentioning

confidence: 99%

Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms

Schaub

Looser

et al. 2010

Blood

162

127

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“…In human sporadic MPN, other genetic events preceding JAK2 V617F are suspected from clonal analysis, using the X chromosome activation or the 20qdel chromosomal abnormality, 1 and secondary JAK2 WT AML progressing from JAK2 V617F MPN. 23,24 Indeed, TET2 mutations might be instrumental in amplifying immature myeloid cells, as suggested by several reports on human samples. 17,23 However, is it necessary for PV occurrence?…”

Section: Tet2 Function In Normal Hematopoiesis and Mpnmentioning

confidence: 86%

“…23,24 Indeed, TET2 mutations might be instrumental in amplifying immature myeloid cells, as suggested by several reports on human samples. 17,23 However, is it necessary for PV occurrence? The absence of TET2 mutations is reported in most PV patients and in vitro or in vivo mouse SCID clonal amplification seems to be missing in those patients lacking TET2 mutations, as suggested by Swierczek and colleagues.…”

Section: Tet2 Function In Normal Hematopoiesis and Mpnmentioning

confidence: 86%

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JAK2V617F/TET2 mutations: does the order matter?

Pronier¹,

Quivoron²,

Bernard³

et al. 2011

Haematologica

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“…(Delhommeau, et al 2009) Subsequent studies confirmed this mutation in MDS, MPN, MDS/MPN, and secondary AML, with frequencies around 10% to 26%, 7% to 13%, 22% to 58% and 24% to 32%, respectively. (Bacher, et al 2010, Couronne, et al 2010, Flach, et al 2010, Jankowska, et al 2009, Kosmider, et al 2009a, Kosmider, et al 2009b, Langemeijer, et al 2009, Saint-Martin, et al 2009, Schaub, et al 2010, Smith, et al 2010, Tefferi, et al 2009a, Tefferi, et al 2009b TET2 mutation occurs in 18.0% to 23% of CN-AML patients. (Chou, et al 2011a, Metzeler, et al 2011 It is closely associated with older age, higher WBC count, but mutually exclusive with IDH mutation.…”

Section: Tet2 Mutationsmentioning

confidence: 99%