A study of KIT activating mutations in acute myeloid leukemia M0 subtype in north India

Hussain, Syed Rizwan; Naqvi, Hena; Singh, Pradyumn; Babu, Sunil G.; Mahdi, Farzana

doi:10.1016/j.ejmhg.2012.01.004

Cited by 2 publications

(5 citation statements)

References 22 publications

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“…The most common mutations were located at point 816 on aspartic acid [36]. Additional point mutations found in past clinical trials [1,4,36], as well as those found in the COSMIC database (https: //cancer.sanger.ac.uk/cosmic, (accessed on 2 June 2022)) [37] were used to obtain mutated KIT gene sequences. Figure 8 shows where the 24 mutations we observed are located on the KIT gene.…”

Section: Finding Prevalent Point Mutations On the Kit Genementioning

confidence: 99%

“…Common mutations that cause AML are in the genes Nucleophosmin 1 (NPM1), FMS-like tyrosine kinase 3 (FLT3), Runt-related transcription factor (RUNX1), and KIT, all of which are critical for hematopoiesis. The KIT gene encodes for a type III receptor tyrosine kinase that is critical for pathways involved in cell proliferation, survival, and Pharmaceuticals 2023, 16, 932 2 of 23 differentiation of hematopoietic progenitor cells [4]. Synonyms for the KIT gene include c-kit, CD117, and mast/stem cell growth factor receptor (SCFR).…”

Section: Introductionmentioning

confidence: 99%

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A Peptide Vaccine Design Targeting KIT Mutations in Acute Myeloid Leukemia

2023

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Acute myeloid leukemia (AML) is a leading blood cancer subtype that can be caused by 27 gene mutations. Previous studies have explored potential vaccine and drug treatments against AML, but many were proven immunologically insignificant. Here, we targeted this issue and applied various clinical filters to improve immune response. KIT is an oncogenic gene that can cause AML when mutated and is predicted to be a promising vaccine target because of its immunogenic responses when activated. We designed a multi-epitope vaccine targeting mutations in the KIT oncogene using CD8+ and CD4+ epitopes. We selected the most viable vaccine epitopes based on thresholds for percentile rank, immunogenicity, antigenicity, half-life, toxicity, IFNγ release, allergenicity, and stability. The efficacy of data was observed through world and regional population coverage of our vaccine design. Then, we obtained epitopes for optimized population coverage from PCOptim-CD, a modified version of our original Java-based program code PCOptim. Using 24 mutations on the KIT gene, 12 CD8+ epitopes and 21 CD4+ epitopes were obtained. The CD8+ dataset had a 98.55% world population coverage, while the CD4+ dataset had a 65.14% world population coverage. There were five CD4+ epitopes that overlapped with the top CD8+ epitopes. Strong binding to murine MHC molecules was found in four CD8+ and six CD4+ epitopes, demonstrating the feasibility of our results in preclinical murine vaccine trials. We then created three-dimensional (3D) models to visualize epitope–MHC complexes and TCR interactions. The final candidate is a non-toxic and non-allergenic multi-epitope vaccine against KIT mutations that cause AML. Further research would involve murine trials of the vaccine candidates on tumor cells causing AML.

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Section: Finding Prevalent Point Mutations On the Kit Genementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Peptide Vaccine Design Targeting KIT Mutations in Acute Myeloid Leukemia

2023

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“…In addition, FLT3 ITD mutated cases showed a significantly low complete remission rate; Both findings are in concordance with the literature. [2][3][4][5][6] The single case of coexistent C-kit D816V mutation and FLT3-D835 mutation in AML with inv (16) has not been previously reported in the literature as far as our knowledge. Further studies are required to elucidate their incidence and prognostic significance which appears to be good in the single case found in our study.…”

Section: Discussionmentioning

confidence: 77%

“…FLT3 mutation including both ITD and TKD has an overall bad prognosis across various cytogenetic abnormalities. 1,[3][4][5][6][7][8] Even though C-kit mutations has no stand-alone prognostic significance in inv (16), it has a worse prognosis in t (8;21). Multiple studies show contradictory results for C-kit mutation in relation to prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…Also, literature is lacking in terms of C-kit and FLT3 mutation status in Indian patients and their prognosis. 4,9 We carried out our study to assess the correlation between French American British (FAB) AML classification and specific cytogenetic abnormalities with Ckit and FLT3 mutation in AML. Also, we wanted to evaluate the prognosis and survival of AML patients with respect to cytogenetic abnormalities and C-kit and FLT3 mutation status.…”

Section: Introductionmentioning

confidence: 99%

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C-Kit and Flt3 mutation status in acute myeloid leukaemia with cytogenetic correlation and prognosis: A series of 75 cases

Parikh,

Dhandapani,

Shankaralingappa

et al. 2023

JDPO

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Recent WHO classification (5 edition) has included Acute Myeloid Leukaemia (AML) with mutations in NPM1, CEBPA as separate entities along with AML with cytogenetic abnormalities in AML with recurrent genetic abnormalities. Even though C-kit and FLT3 mutations in AML have no diagnostic importance, prognostic significance in different subtypes of AML for the presence of these mutations are not the same.To assess the correlation between French American British (FAB) AML classification, specific cytogenetic abnormalities with C-kit, and FLT3 mutation in AML and to evaluate the prognosis and survival of AML patients with respect to cytogenetic abnormalities and C-kit and FLT3 mutation status. Retrospectively all AML cases in which C-kit and FLT3 mutation status was assessed were retrieved; C-kit D816V mutation status had been assessed by Real time PCR; For FLT3 mutation, both Internal tandem duplication (ITD) and D835V mutation status had been assessed using PCR and gel electrophoresis; The data regarding morphological with immunophenotypic diagnosis, conventional karyotyping, FISH for translocation 8;21 (t (8;21)) and inversion16 / translocation16;16 (t (16;16) were also retrieved in all these cases along with follow-up from hospital records. Total 75 cases were included; Male/ Female ratio was 1.21:1 (41/34); Median age was 31 (Range: 2 - 64); 18 cases had translocation 8;21 (t (8;21)); 3 cases showed inversion16 / translocation16;16 (t (16;16); Out of the 18 cases which showed t (8;21), 10 cases had associated loss of sex chromosome. Eight cases had C-kit D816V mutation; three of which had t (8;21) while two had inversion 16. 12 cases had FLT3 mutations among which nine were ITD while three had D835V mutation. On karyotyping, one of these cases showed hyperdiploidy while the majority had normal karyotype. A single case had both C-kit D816V mutation and FLT3 D835V mutation with inversion 16 on karyotyping; Most common type of AML in both cases with FLT3 mutation and C-kit mutation was AML-M2 (FAB); Commonest karyotyping abnormality for cases with C-kit mutation was t(8;21); while for FLT3 mutation, the majority had normal karyotype; The single case which had both C-kit D816V mutation and FLT3 D835V mutation was alive event-free at three-year follow-up. Both FLT3 ITD and TKD mutations had a worse prognosis in our study. However, AML cases with C-kit mutation had a similar prognosis comparable to C kit negative cases. A large-scale study is required to elucidate the significance of this.

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A study of KIT activating mutations in acute myeloid leukemia M0 subtype in north India

Cited by 2 publications

References 22 publications

A Peptide Vaccine Design Targeting KIT Mutations in Acute Myeloid Leukemia

A Peptide Vaccine Design Targeting KIT Mutations in Acute Myeloid Leukemia

C-Kit and Flt3 mutation status in acute myeloid leukaemia with cytogenetic correlation and prognosis: A series of 75 cases

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