Mutation analysis of therapy-related myeloid neoplasms

Nishiyama, Takahiro; Ishikawa, Yuichi; Kawashima, Naomi; Akashi, Akimi; Adachi, Yayoi; Hattori, Hitoshi; Ushijima, Yoko; Kiyoi, Hitoshi

doi:10.1016/j.cancergen.2018.02.006

Cited by 12 publications

(10 citation statements)

References 24 publications

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“…In addition, we analyzed mutations in 49 other genes in 170 patients using the TruSight Myeloid Sequencing Panel (Illumina, San Diego, CA), as previously reported (supplemental Table 2). 8,25…”

Section: Cytogenetic and Molecular Analysesmentioning

confidence: 99%

Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11

et al. 2020

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Section: Cytogenetic and Molecular Analysesmentioning

confidence: 99%

Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11

et al. 2020

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“…Our data are in line with recently published data by Young et al 35 who found a factor 5.4 increase in the risk of developing AML associated with detectable CH at a VAF of $0.01, as well as the ability to detect the presence of low VAF mutations several years before onset of tMN. 36,37 To the best of our knowledge, the current study is the first to show that aberrant CD7 expression on the stem cell population from leukapheresis products is associated with an almost sevenfold increase in risk of developing tMN. Furthermore, we found that patients with tMN were poorer stem cell mobilizers during leukapheresis compared with control subjects.…”

Section: Discussionmentioning

confidence: 70%

Clonal hematopoiesis predicts development of therapy-related myeloid neoplasms post–autologous stem cell transplantation

Soerensen¹,

Aggerholm²,

Kerndrup

et al. 2020

Blood Advances

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Therapy-related myeloid neoplasms (tMN) develop after exposure to cytotoxic and radiation therapy, and due to their adverse prognosis, it is of paramount interest to identify patients at high risk. The presence of clonal hematopoiesis has been shown to increase the risk of developing tMN. The value of analyzing hematopoietic stem cells harvested at leukapheresis before autologous stem cell transplantation (ASCT) with next-generation sequencing and immunophenotyping represents potentially informative parameters that have yet to be discovered. We performed a nested case-control study to elucidate the association between clonal hematopoiesis, mobilization potential, and aberrant immunophenotype in leukapheresis products with the development of tMN after ASCT. A total of 36 patients with nonmyeloid disease who were diagnosed with tMN after treatment with ASCT were included as case subjects. Case subjects were identified from a cohort of 1130 patients treated with ASCT and matched with 36 control subjects who did not develop tMN after ASCT. Case subjects were significantly poorer mobilizers of CD34+ cells at leukapheresis (P = .016), indicating that these patients possess inferior bone marrow function. Both clonal hematopoiesis (odds ratio, 5.9; 95% confidence interval, 1.8-19.1; P = .003) and aberrant expression of CD7 (odds ratio, 6.6; 95% confidence interval, 1.6-26.2; P = .004) at the time of ASCT were associated with an increased risk of developing tMN after ASCT. In conclusion, clonal hematopoiesis, present at low variant allele frequencies, and aberrant CD7 expression on stem cells in leukapheresis products from patients with nonmyeloid hematologic cancer hold potential for the early identification of patients at high risk of developing tMN after ASCT.

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“…Especially, TP53-mutant clones induce progress to therapyrelated MDS/AML. Therapy-related myeloid neoplasms have mutations in TP53 and epigenetic modifying genes, instead of mutations in tyrosine kinase and spliceosome genes [16]. The possible treatments are now the use of hypomethylating agents or in future anti-inflammatory therapy and clonally selective immunotherapies.…”

Section: Advances In Our Knowledge Of Cytogenetic Abnormalities and Gmentioning

confidence: 99%

Introductory Chapter: Progress in Myelodysplastic Syndrome Area

Fuchs¹

2019

Recent Developments in Myelodysplastic Syndromes

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Mutation analysis of therapy-related myeloid neoplasms

Cited by 12 publications

References 24 publications

Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11

Prospective evaluation of prognostic impact of KIT mutations on acute myeloid leukemia with RUNX1-RUNX1T1 and CBFB-MYH11

Clonal hematopoiesis predicts development of therapy-related myeloid neoplasms post–autologous stem cell transplantation

Introductory Chapter: Progress in Myelodysplastic Syndrome Area

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