Zhang X, Zhang X, Li X, Lv Y, Zhu Y, Wang J, et al. CEBPA mutation was the most common co-mutation that occurred alongside IKZF1 mutation in AML. IKZF1 aberration conferred poor prognosis in ALL, but only a high burden of IKZF1 mutation predicted poor OS in AML because IKZF1 mutation with VAF < 10% accounted for 35% of all IKZF1 MUT patients, and IKZF1 mutation contributed less to disease than other mutations did in this group of patients. Missense mutation accounted for nearly half of IKZF1 mutations, and it almost affected the DNA-binding domain in AML, while its DNA-binding domain and dimerization domain involvement was relatively balanced in ALL. Unlike in ALL, IKZF1 mutation and deletion were equally dominant in AML. IKZF1 deletion, caused by -7/monosomy 7, was detected in 3.20% of our patients. This may be because patients were of different races or it may be because of differences in sequencing depth. 1H, I).Ĭompared with foreign cohorts (OHSU, 1.35% TCGA, 0.5% TARGET, 4.21%), the frequency of IKZF1 mutation was relatively high (3.83%). IKZF1 mutation combined with SF3B1 mutation conferred extremely poor OS on AML, but the RFS of IKZF1 MUT/ SF3B1 MUT AML patients was unavailable because no patient reached CR (Fig. None of these patients achieved CR at any point during the regimen (Additional file 9: Table S6). IKZF1 WT/ SF3B1 MUT AML patients exhibited a CR rate of 50%, and the therapeutic response was even worse in IKZF1 MUT/ SF3B1 MUT AML. IKZF1 mutation conferred a relatively low CR in the CEBPA WT /non- CEBPA bZIP−inf−MUT group, but not in the CEBPA bZIP−inf−MUT group (Additional file 8: Table S5), and it influenced OS and RFS in the CEBPA WT /non- CEBPA bZIP−inf−MUT group but not in the CEBPA bZIP−inf−MUT group (Additional file 3: Fig S3C, D). In IKZF1 MUT patients, CEBPA bZIP−inf mutation (83.3%) was more common than non- CEBPA bZIP−inf mutation (16.7%). IKZF1 mutation did not influence OS or RFS in CSF3R WT and CSF3R MUT (Additional file 3: Fig S3A, B, Additional file 7: Table S4). The prognostic role of CEBPA bZIP−inf, SF3B1, and CSF3R mutations was revealed in our cohort (Additional file 2: Fig S2). We also performed subgroup survival analysis. IKZF1 mutation exhibited concurrences with CEBPA, SF3B1, and CSF3R mutations, but it was mutually exclusive with NPM1 mutation (Fig. We also analyzed the relationships among IKZF1 mutation and other gene mutations. ( H, I) The prognostic role of combined IKZF1 and SF3B1 mutations on AML was investigated, and the OS ( H) as well as RFS ( I) of AML with different IKZF1 or SF3B1 mutated status are exhibited ( G) The distribution of frequent AML-associated gene mutations in IKZF1 WT and IKZF1 MUT groups, and the count as well as percentage of each gene mutation are shown. ( F) The difference of additional mutations distribution in IKZF1 WT and IKZF1 MUT groups, and the percentage of each gene mutation is exhibited. ( D, E) The influence of IKZF1 mutation burden on the prognosis of AML was studied, and the OS ( D) as well as RFS ( E) of IKZF1 WT, IKZF1 MUT with VAF > 0.20, and IKZF1 MUT with VAF ≤ 0.20 groups are shown. ( B, C) The OS ( B) and RFS ( C) of IKZF1 WT and IKZF1 MUT groups in our AML cohort. The nonsense or frameshift mutation was marked as red, while the missense mutation was marked as blue. ( A) The distribution of IKZF1 mutations, which were identified in our cohort, on the protein. We believe this work improves our knowledge of IKZF1 mutation. In subgroup analysis, our results showed that IKZF1 mutation conferred poor therapeutic response and prognosis for SF3B1-mutated AML (P = 0.0017). IKZF1 mutation showed significant co-occurrences with CEBPA (P 0.20) showed relatively short overall survival period (P = 0.012), and it was an independent factor for the increased risk of death (hazard ratio, 6.101 95% CI 2.278–16.335 P = 0.0003). The baseline characteristics of IKZF1-mutated and wild-type patients were comparable. This condition has a young median age of onset of morbidity (P = 0.032). A total of 26 IKZF1 mutations were found in 20 AML patients (20/522, 3.83%). Herein, we attempt to answer this question in one relatively large cohort covering 522 newly diagnosed AML patients. In a previous work, we described the distribution pattern of IKZF1 mutation in AML, but its clinical impact has remained undefined due to the limited number of cases. Knowledge of the IKZF1 mutation in AML specifically is extremely limited. Genetic heterogeneity poses a great challenge to the understanding and management of acute myeloid leukemia (AML).
0 Comments
Leave a Reply. |