1Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
2The Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada
3Department of Computer Science, University of Toronto, Toronto, Canada
4Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Hwasun, Korea
5Division of Hematology-Oncology, Samsung Medical Center, Seoul, Korea
6Department of Hematology, Cancer Research Institute, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
7Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, Korea
8Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, Korea
9Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, Korea
10Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
Copyright © 2023 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
The study was approved by the Institutional Review Board (IRB) of Chonnam National University Hwasun Hospital, Korea (IRB reference number: CNUHH-2014-153). All study participants provided written informed consent.
Author Contributions
Conceived and designed the analysis: Ahn SY, Kim HJ (Hyeoung-Joon Kim), Ahn JS, Kim DDH.
Collected the data: Ahn SY, Kim M, Song GY, Jung SH, Yang DH, Lee JJ, Kim MY, Jung CW, Jang JH, Kim HJ (Hee Je Kim), Moon JH, Sohn SK, Won JH, Kim SH, Ahn JS, Kim DDH.
Contributed data or analysis tools: Ahn SY, Kim T, Ahn JS, Kim DDH.
Performed the analysis: Ahn SY, Kim T, Ahn JS.
Wrote the paper: Ahn SY, Ahn JS.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Parameter | Median or frequency (n=395) | CEBPAwild (n=317) | bZIPin-f CEBPA mutations (n=50) | Non-bZIPin-f CEBPA mutations (n=28) | p-valuea) (wild vs. bZIPin-f) | p-valueb) (wild vs. non-bZIPin-f) | p-valuec) (bZIPin-f vs. non-bZIPin-f) |
---|---|---|---|---|---|---|---|
Age (yr) | 52 (15–84) | 54 (15–84) | 38 (15–67) | 57 (17–75) | < 0.001d) | 0.793 | 0.001d) |
Male sex | 201 (50.9) | 161 (50.3) | 23 (63.0) | 17 (43.1) | 0.547 | 0.332 | 0.244 |
WBC (×109/L) | 28.2 (0.3–397.2) | 27.1 (0.3–384.0) | 31.6 (2.0–333.2) | 49.8 (1.7–397.2) | 0.142 | 0.031d) | 0.327 |
Bone marrow blasts (%) | 63 (3–100) | 70 (3–100) | 82 (21–100) | 70 (30–100) | 0.135 | 0.231 | 0.964 |
NPM1mut | 128 (32.4) | 117 (36.9) | 2 (4.0) | 9 (32.1) | < 0.001d) | 0.686 | 0.001d) |
FLT3-ITDmut | 107 (27.1) | 93 (29.3) | 5 (10.0) | 9 (32.1) | 0.003d) | 0.829 | 0.028d) |
DNMT3Amut | 95 (24.1) | 87 (27.4) | 5 (10.0) | 3 (10.7) | 0.008d) | 0.070 | > 0.99 |
NRASmut | 68 (17.2) | 57 (18.0) | 8 (16.0) | 3 (10.7) | 0.844 | 0.440 | 0.737 |
IDH2mut | 55 (13.9) | 48 (15.1) | 3 (6.0) | 4 (14.3) | 0.120 | > 0.99 | 0.243 |
PTPN11mut | 36 (9.1) | 32 (10.1) | 2 (4.0) | 2 (7.1) | 0.289 | > 0.99 | 0.615 |
FLT3-TKDmut | 33 (8.4) | 32 (10.1) | 1 (2.0) | 0 | 0.065 | 0.092 | > 0.99 |
IDH1mut | 32 (8.1) | 31 (9.8) | 0 | 1 (3.6) | 0.013d) | 0.494 | 0.359 |
TET2mut | 27 (6.8) | 20 (6.3) | 3 (6.0) | 4 (14.3) | > 0.99 | 0.118 | 0.243 |
KRASmut | 22 (5.6) | 19 (6.0) | 2 (4.0) | 1 (3.6) | 0.752 | > 0.99 | > 0.99 |
SRSF2mut | 21 (5.3) | 19 (6.0) | 1 (2.0) | 1 (3.6) | 0.497 | > 0.99 | > 0.99 |
GATA2mut | 16 (4.1) | 9 (2.8) | 5 (10.0) | 2 (7.1) | 0.029d) | 0.222 | > 0.99 |
Achieved CR | 325 (82.3) | 252 (79.5) | 47 (94.0) | 26 (92.9) | 0.011d) | 0.131 | > 0.99 |
Received allo-HCT in CR achieved patients (n=325) | 127 (39.1) | 91 (36.1) | 26 (52.0) | 10 (35.7) | 0.015d) | > 0.99 | 0.223 |
Values are presented as median (range) or number (%). Allo-HCT, allogeneic hematopoietic cell transplantation; bZIPin-f CEBPA, bZIP in-frame CEBPA mutation; CEBPA, CCAAT/enhancer-binding protein α; CEBPAwild, CEBPA wild-type; CR, complete remission; non-bZIPin-f CEBPA, non bZIP or non-in-frame CEBPA mutation; WBC, white blood cell.
a) The p-values refer to comparisons among groups with CEBPAwild and bZIPin-f CEBPA,
b) The p-values refer to comparisons among groups with CEBPAwild and non-bZIPin-f CEBPA,
c) The p-values refer to comparisons between those with bZIPin-f CEBPA and non-bZIPin-f CEBPA,
d) Significant variables are shown.
Allo-HCT, allogeneic hematopoietic cell transplantation; bZIPin-f CEBPA, bZIP in-frame CEBPA mutation; CEBPA, CCAAT/enhancer-binding protein α; CI, confidence internal; CIR, cumulate incidence of relapse; CR, complete remission; HR, hazard ratio; OR, odd ratio; OS, overall survival; RFS, relapse-free survival.
No. of CEBPA mutation | Location and type of mutation | CR achieved (%) | Consolidation type | |
---|---|---|---|---|
Chemotherapy alone | Allo-HCT | |||
Wild (n=317) | Wild (n=317) | 252 (79.5) | 135 | 90 |
Double (n=51) | bZIPin-f (n=41) | 40 (98.0) | 15 | 24 |
Non-bZIPin-f (n=10) | 10 (100) | 3 | 5 | |
Single (n=27) | bZIPin-f (n=9) | 7 (78.0) | 3 | 2 |
Non-bZIPin-f (n=18) | 16 (89.0) | 10 | 5 |
Allo-HCT, allogeneic hematopoietic cell transplantation; bZIPin-f, basic leucine zipper in-frame CEBPA mutation; CEBPA, CCAAT/enhancer-binding protein α; CR, complete remission; non-bZIPin-f, non bZIP or non-inframe CEBPA mutation.
Parameter | Median or frequency (n=395) | CEBPAwild (n=317) | bZIPin-f CEBPA mutations (n=50) | Non-bZIPin-f CEBPA mutations (n=28) | p-value |
p-value |
p-value |
---|---|---|---|---|---|---|---|
Age (yr) | 52 (15–84) | 54 (15–84) | 38 (15–67) | 57 (17–75) | < 0.001 |
0.793 | 0.001 |
Male sex | 201 (50.9) | 161 (50.3) | 23 (63.0) | 17 (43.1) | 0.547 | 0.332 | 0.244 |
WBC (×109/L) | 28.2 (0.3–397.2) | 27.1 (0.3–384.0) | 31.6 (2.0–333.2) | 49.8 (1.7–397.2) | 0.142 | 0.031 |
0.327 |
Bone marrow blasts (%) | 63 (3–100) | 70 (3–100) | 82 (21–100) | 70 (30–100) | 0.135 | 0.231 | 0.964 |
NPM1mut | 128 (32.4) | 117 (36.9) | 2 (4.0) | 9 (32.1) | < 0.001 |
0.686 | 0.001 |
FLT3-ITDmut | 107 (27.1) | 93 (29.3) | 5 (10.0) | 9 (32.1) | 0.003 |
0.829 | 0.028 |
DNMT3Amut | 95 (24.1) | 87 (27.4) | 5 (10.0) | 3 (10.7) | 0.008 |
0.070 | > 0.99 |
NRASmut | 68 (17.2) | 57 (18.0) | 8 (16.0) | 3 (10.7) | 0.844 | 0.440 | 0.737 |
IDH2mut | 55 (13.9) | 48 (15.1) | 3 (6.0) | 4 (14.3) | 0.120 | > 0.99 | 0.243 |
PTPN11mut | 36 (9.1) | 32 (10.1) | 2 (4.0) | 2 (7.1) | 0.289 | > 0.99 | 0.615 |
FLT3-TKDmut | 33 (8.4) | 32 (10.1) | 1 (2.0) | 0 | 0.065 | 0.092 | > 0.99 |
IDH1mut | 32 (8.1) | 31 (9.8) | 0 | 1 (3.6) | 0.013 |
0.494 | 0.359 |
TET2mut | 27 (6.8) | 20 (6.3) | 3 (6.0) | 4 (14.3) | > 0.99 | 0.118 | 0.243 |
KRASmut | 22 (5.6) | 19 (6.0) | 2 (4.0) | 1 (3.6) | 0.752 | > 0.99 | > 0.99 |
SRSF2mut | 21 (5.3) | 19 (6.0) | 1 (2.0) | 1 (3.6) | 0.497 | > 0.99 | > 0.99 |
GATA2mut | 16 (4.1) | 9 (2.8) | 5 (10.0) | 2 (7.1) | 0.029 |
0.222 | > 0.99 |
Achieved CR | 325 (82.3) | 252 (79.5) | 47 (94.0) | 26 (92.9) | 0.011 |
0.131 | > 0.99 |
Received allo-HCT in CR achieved patients (n=325) | 127 (39.1) | 91 (36.1) | 26 (52.0) | 10 (35.7) | 0.015 |
> 0.99 | 0.223 |
Values are presented as median (range) or number (%). Allo-HCT, allogeneic hematopoietic cell transplantation; bZIPin-f CEBPA, bZIP in-frame CEBPA mutation; CEBPA, CCAAT/enhancer-binding protein α; CEBPAwild, CEBPA wild-type; CR, complete remission; non-bZIPin-f CEBPA, non bZIP or non-in-frame CEBPA mutation; WBC, white blood cell.
a)The p-values refer to comparisons among groups with CEBPAwild and bZIPin-f CEBPA,
b)The p-values refer to comparisons among groups with CEBPAwild and non-bZIPin-f CEBPA,
c)The p-values refer to comparisons between those with bZIPin-f CEBPA and non-bZIPin-f CEBPA,
d)Significant variables are shown.
Parameter | Variable | Multivariate | ||
---|---|---|---|---|
OR/HR | 95% CI | p-value | ||
CR achieve | Age < 60 yr | 2.93 | 1.69–5.09 | 0.001 |
NPM1mut | 2.48 | 1.31–4.67 | 0.005 | |
bZIPin-f CEBPA | 3.97 | 1.16–13.50 | 0.028 | |
PTPN11mut | 0.37 | 0.17–0.81 | 0.013 | |
OS Allo-HCT | 0.61 | 0.44–0.85 | 0.003 | |
bZIPin-f CEBPA | 0.49 | 0.30–0.81 | 0.006 | |
NPM1mut | 0.57 | 0.41–0.80 | < 0.001 | |
FLT3-ITDmut | 1.97 | 1.43–2.71 | < 0.001 | |
RFS Allo-HCT | 0.63 | 0.45–0.87 | 0.006 | |
bZIPin-f CEBPA | 0.56 | 0.35–0.91 | 0.019 | |
FLT3-ITDmut | 1.64 | 1.21–2.23 | 0.001 | |
CIR Allo-HCT | 0.41 | 0.28–0.60 | < 0.001 | |
bZIPin-f CEBPA | 0.49 | 0.25–0.96 | 0.036 | |
FLT3-ITDmut | 1.78 | 1.23–2.59 | 0.002 |
Allo-HCT, allogeneic hematopoietic cell transplantation; bZIPin-f CEBPA, bZIP in-frame CEBPA mutation; CEBPA, CCAAT/enhancer-binding protein α; CI, confidence internal; CIR, cumulate incidence of relapse; CR, complete remission; HR, hazard ratio; OR, odd ratio; OS, overall survival; RFS, relapse-free survival.
Allo-HCT, allogeneic hematopoietic cell transplantation; bZIPin-f, basic leucine zipper in-frame
Values are presented as median (range) or number (%). Allo-HCT, allogeneic hematopoietic cell transplantation; bZIPin-f The p-values refer to comparisons among groups with The p-values refer to comparisons among groups with The p-values refer to comparisons between those with bZIPin-f Significant variables are shown.
Allo-HCT, allogeneic hematopoietic cell transplantation; bZIPin-f