Possible co-existence of RAS activation and monosomy 7 in the leukaemic transformation of myelodysplastic syndromes

Stephenson, J; He, Lizhen; Mufti, Ghulam J.

doi:10.1016/0145-2126(95)00056-t

Cited by 28 publications

(11 citation statements)

References 27 publications

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“…NRAS mutations were further shown to be associated with karyotype evolution, e.g. with the acquisition of monosomy 7, during MDS transformation, 59,60 and with inferior survival in MDS. 57 Based on these results the inclusion of NRAS-screening at diagnosis and during follow-up in MDS might be discussed.…”

Section: Discussionmentioning

confidence: 99%

A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia

Bacher¹,

Haferlach²,

Kern³

et al. 2007

Haematologica

142

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Section: Discussionmentioning

confidence: 99%

A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia

Bacher¹,

Haferlach²,

Kern³

et al. 2007

Haematologica

142

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“…Two main cytogenetic pathways have been proposed to explain the malignant transformation step in patients with therapy-related MDS (t-MDS): [29][30][31] pathway I is 'À7/7q-with normal chromosome 5', and pathway II is 'À5/5q-'. The patients belonging to the pathway I group frequently show mutations of RAS genes 32 and methylation of the p15 INK4b gene promoter. 33 A more recent study has shown that AML1 mutations in patients with t-MDS were highly significantly associated with À7/7q-.…”

Section: Discussionmentioning

confidence: 99%

Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations

Niimi

Harada

et al. 2006

Leukemia

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AML1/RUNX1 mutations have been reported frequently in myelodysplastic syndrome (MDS) patients, especially those diagnosed with refractory anemia with excess blast (RAEB), RAEB in transformation (RAEBt), or AML following MDS (these categories are defined as MDS/AML). Although AML1 mutations are suspected to play a pivotal role in the development of MDS/ AML, acquisition of additional genetic alterations is also necessary. We analyzed gene alterations in MDS/AML patients with AML1 mutations, comparing them to alterations in those without an AML1 mutation. AML1 mutations were significantly associated with À7/7q-, whereas MDS/AML patients without AML1 mutations showed a high frequency of À5/5q-and a complex karyotype. Patients with AML1 mutations showed more mutations of their FLT3, N-RAS, PTPN11, and NF1 genes, resulting in a significantly higher mutation frequency for receptor tyrosine kinase (RTK)-RAS signaling pathways in AML1-mutated MDS/AML patients compared to AML1-wild-type MDS/AML patients (38% versus 6.3%, Po0.0001). Conversely, p53 mutations were detected only in patients without AML1 mutations. Furthermore, blast cells of the AML1-mutated patients expressing surface c-KIT, and SHP-2 mutants contributed to prolonged and enhanced extracellular signalregulated kinase activation following stem cell factor stimulation. Our results suggest that MDS/AML arising from AML1/ RUNX1 mutations has a significant association with À7/7q-alteration, and frequently involves RTK-RAS signaling pathway activation.

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“…Although the prognosis of patients belonging to pathway I is generally poor, some cases of t-MDS with monosomy 7 as the sole abnormality, only a modest cytopenia, and without an excess of blasts in the bone marrow may survive even for years on supportive therapy only. 15 Mutations of the RAS genes 16,17 and methylation of the of the p15 gene promotor (D.H.C., J.P.-B., manuscript submitted) have been observed frequently in this pathway, but they probably do not represent primary genetic abnormalities in leukemic transformation. Mutations of p53 are not very common.…”

Section: Revised Model For Cytogenetic and Genetic Pathways In T-mds mentioning

confidence: 99%

Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia

Pedersen‐Bjergaard

Andersen

Christiansen

et al. 2002

Blood

227

130

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Therapy-related acute myeloid leukemia (t-AML) in most cases develops after chemotherapy of other malignancies and shows characteristic chromosome aberrations. Two general types of t-AML have previously been identified. One type is observed after therapy with alkylating agents and characteristically presents as therapy-related myelodysplasia with deletions or loss of the long arms of chromosomes 5 and 7 or loss of the whole chromosomes. The other type is observed after therapy with topoisomerase II inhibitors and characteristically presents as overt t-AML with recurrent balanced chromosome aberrations. Recent research suggests that these 2 general types of t-AML can now be subdivided into at least 8 genetic pathways with a different etiology and different biologic characteristics. (Blood.

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Possible co-existence of RAS activation and monosomy 7 in the leukaemic transformation of myelodysplastic syndromes

Cited by 28 publications

References 27 publications

A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia

A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia

Hyperactivation of the RAS signaling pathway in myelodysplastic syndrome with AML1/RUNX1 point mutations

Genetic pathways in therapy-related myelodysplasia and acute myeloid leukemia

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