Limits...
Incidences and Prognostic Impact of c-KIT, WT1, CEBPA, and CBL Mutations, and Mutations Associated With Epigenetic Modification in Core Binding Factor Acute Myeloid Leukemia: A Multicenter Study in a Korean Population.

Park SH, Lee HJ, Kim IS, Kang JE, Lee EY, Kim HJ, Kim YK, Won JH, Bang SM, Kim H, Song MK, Chung JS, Shin HJ - Ann Lab Med (2015)

Bottom Line: Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared.However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly.The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.

ABSTRACT

Background: To identify potential molecular prognostic markers in core binding factor (CBF) AML, we analyzed incidences and prognostic impacts of mutations in c-KIT, WT1, CEBPA, CBL, and a number of epigenetic genes in CBF AML.

Methods: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared.

Results: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (≤5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014).

Conclusions: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.

No MeSH data available.


Related in: MedlinePlus

Comparisons of overall survival and disease free survival lengths in core binding factor acute leukemia patients with t(8;21) and no FLT3 ITD or NPM1 mutations, between patients with c-KIT mutations and those without c-KIT mutations (N=69, A, overall survival; B, disease free survival). Identical comparisons between patients with WT1 mutations and those without WT1 mutations (N=58, C, overall survival; D, disease free survival) are also given in this figure.Abbreviation: WT, Wilms' tumor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4390696&req=5

Figure 1: Comparisons of overall survival and disease free survival lengths in core binding factor acute leukemia patients with t(8;21) and no FLT3 ITD or NPM1 mutations, between patients with c-KIT mutations and those without c-KIT mutations (N=69, A, overall survival; B, disease free survival). Identical comparisons between patients with WT1 mutations and those without WT1 mutations (N=58, C, overall survival; D, disease free survival) are also given in this figure.Abbreviation: WT, Wilms' tumor.

Mentions: Patients with t(8;21) for whom c-KIT and WT1 mutation data were available (71 and 60 patients, respectively) were categorized into two subgroups based on their c-KIT and WT1 mutation status, and their clinical features were compared. c-KIT and WT1 were selected because they showed higher mutation frequencies than other genes. To evaluate the prognostic impact of both c-KIT and WT1 mutations, both overall survival (OS) and disease free survival (DFS) were compared between the two patient subgroups. Since two patients showed FLT3 ITD or NPM1 mutations, they were excluded from the survival analysis to exclude the prognostic impact of these mutations. OS was defined as the time from diagnosis to death or last follow-up. DFS was defined as the time from CR to relapse (for patients who experienced relapse), death (for non-relapsed patients who did not survive), or last follow-up (for non-relapsed patients who survived). Patients who underwent SCT were censored at the time of transplantation. In addition, identical comparisons were performed for 21 patients with inv(16). These results are summarized in Table 3 and Fig. 1.


Incidences and Prognostic Impact of c-KIT, WT1, CEBPA, and CBL Mutations, and Mutations Associated With Epigenetic Modification in Core Binding Factor Acute Myeloid Leukemia: A Multicenter Study in a Korean Population.

Park SH, Lee HJ, Kim IS, Kang JE, Lee EY, Kim HJ, Kim YK, Won JH, Bang SM, Kim H, Song MK, Chung JS, Shin HJ - Ann Lab Med (2015)

Comparisons of overall survival and disease free survival lengths in core binding factor acute leukemia patients with t(8;21) and no FLT3 ITD or NPM1 mutations, between patients with c-KIT mutations and those without c-KIT mutations (N=69, A, overall survival; B, disease free survival). Identical comparisons between patients with WT1 mutations and those without WT1 mutations (N=58, C, overall survival; D, disease free survival) are also given in this figure.Abbreviation: WT, Wilms' tumor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390696&req=5

Figure 1: Comparisons of overall survival and disease free survival lengths in core binding factor acute leukemia patients with t(8;21) and no FLT3 ITD or NPM1 mutations, between patients with c-KIT mutations and those without c-KIT mutations (N=69, A, overall survival; B, disease free survival). Identical comparisons between patients with WT1 mutations and those without WT1 mutations (N=58, C, overall survival; D, disease free survival) are also given in this figure.Abbreviation: WT, Wilms' tumor.
Mentions: Patients with t(8;21) for whom c-KIT and WT1 mutation data were available (71 and 60 patients, respectively) were categorized into two subgroups based on their c-KIT and WT1 mutation status, and their clinical features were compared. c-KIT and WT1 were selected because they showed higher mutation frequencies than other genes. To evaluate the prognostic impact of both c-KIT and WT1 mutations, both overall survival (OS) and disease free survival (DFS) were compared between the two patient subgroups. Since two patients showed FLT3 ITD or NPM1 mutations, they were excluded from the survival analysis to exclude the prognostic impact of these mutations. OS was defined as the time from diagnosis to death or last follow-up. DFS was defined as the time from CR to relapse (for patients who experienced relapse), death (for non-relapsed patients who did not survive), or last follow-up (for non-relapsed patients who survived). Patients who underwent SCT were censored at the time of transplantation. In addition, identical comparisons were performed for 21 patients with inv(16). These results are summarized in Table 3 and Fig. 1.

Bottom Line: Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared.However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly.The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.

ABSTRACT

Background: To identify potential molecular prognostic markers in core binding factor (CBF) AML, we analyzed incidences and prognostic impacts of mutations in c-KIT, WT1, CEBPA, CBL, and a number of epigenetic genes in CBF AML.

Methods: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared.

Results: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (≤5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014).

Conclusions: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.

No MeSH data available.


Related in: MedlinePlus