Distinct FLT3 Pathways Gene Expression Profiles in Pediatric De Novo Acute Lymphoblastic and Myeloid Leukemia with FLT3 Mutations: Implications for Targeted Therapy
Abstract
:1. Introduction
2. Results
2.1. Association of FLT3 Gene Mutations with Clinical Characteristics and Remission Status
2.2. The Characteristics of FLT3 Mutations
2.3. Patterns of Co-Occurrence in FLT3 Gene Mutations
2.4. FLT3 and Their Related Gene Expressions
2.5. Prognostic Impacts of FLT3 Mutations
3. Discussion
4. Methods and Materials
4.1. Participants and Study Design
4.2. Chemotherapy Protocol
4.3. Whole Exome Sequencing
4.4. RNA Sequencing
4.5. Treatment Response
4.6. Follow-Up
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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The Expression Level of Genes (FPKM) | Total (N = 206) | FLT3 Wild-Type (N = 176) | FLT3 Mutant Group (N = 30) | p |
---|---|---|---|---|
FLT3 (median [IQR]) | 31.34 [10.69, 80.33] | 23.11 [9.16, 59.14] | 108.02 [85.11, 142.06] | <0.001 |
KRAS (median [IQR]) | 22.18 [16.46, 30.70] | 22.05 [16.50, 29.30] | 25.03 [16.51, 34.23] | 0.476 |
HRAS (median [IQR]) | 2.72 [2.05, 3.67] | 2.77 [2.08, 3.88] | 2.35 [1.57, 3.16] | 0.044 |
NRAS (median [IQR]) | 33.62 [27.64, 40.39] | 33.46 [28.03, 40.29] | 35.90 [23.78, 42.71] | 0.865 |
PIK3CA (median [IQR]) | 19.99 [15.59, 26.74] | 20.08 [15.73, 27.08] | 18.62 [15.03, 25.17] | 0.355 |
PIK3CB (median [IQR]) | 5.76 [4.50, 7.15] | 5.74 [4.49, 7.16] | 5.83 [4.53, 7.04] | 0.786 |
PIK3CD (median [IQR]) | 29.48 [20.69, 37.98] | 29.63 [21.19, 38.09] | 28.03 [18.95, 34.27] | 0.409 |
PIK3R3 (median [IQR]) | 1.89 [0.90, 3.49] | 2.02 [1.03, 3.84] | 1.33 [0.69, 1.77] | 0.002 |
AKT1 (median [IQR]) | 7.22 [6.04, 9.22] | 7.40 [6.10, 9.23] | 7.09 [5.56, 8.63] | 0.527 |
AKT2 (median [IQR]) | 9.83 [8.21, 11.75] | 10.18 [8.33, 11.79] | 8.53 [7.36, 10.89] | 0.058 |
AKT3 (median [IQR]) | 7.01 [2.77, 12.78] | 6.91 [2.85, 12.67] | 8.50 [2.71, 15.05] | 0.510 |
MTOR (median [IQR]) | 9.90 [8.38, 11.71] | 9.98 [8.53, 11.76] | 9.66 [7.94, 10.84] | 0.267 |
CHUK (median [IQR]) | 8.83 [7.23, 10.21] | 8.78 [7.22, 10.19] | 9.35 [8.38, 10.58] | 0.256 |
IKBKB (median [IQR]) | 7.83 [6.60, 9.50] | 7.87 [6.64, 9.61] | 7.66 [6.39, 8.65] | 0.442 |
IKBKG (median [IQR]) | 0.65 [0.50, 0.97] | 0.64 [0.50, 0.90] | 0.79 [0.51, 1.19] | 0.105 |
BAD (median [IQR]) | 4.20 [3.04, 5.28] | 4.28 [3.11, 5.34] | 3.39 [2.25, 4.52] | 0.018 |
BRAF (median [IQR]) | 15.13 [12.18, 18.94] | 15.15 [12.25, 18.98] | 13.68 [11.77, 18.74] | 0.571 |
RAF1 (median [IQR]) | 19.67 [16.29, 24.23] | 20.09 [16.39, 24.41] | 18.88 [14.94, 21.54] | 0.108 |
MAP2K1 (median [IQR]) | 11.16 [8.73, 14.23] | 11.08 [8.70, 13.32] | 11.90 [8.77, 16.70] | 0.323 |
MAP2K2 (median [IQR]) | 8.00 [6.54, 9.93] | 8.06 [6.88, 10.10] | 6.84 [4.03, 9.53] | 0.017 |
MAPK1 (median [IQR]) | 15.53 [13.36, 18.54] | 15.53 [13.42, 18.67] | 15.54 [13.16, 17.06] | 0.378 |
MAPK3 (median [IQR]) | 5.93 [4.88, 7.14] | 6.01 [5.01, 7.16] | 5.21 [3.92, 6.62] | 0.028 |
STAT3 (median [IQR]) | 13.76 [11.41, 19.61] | 13.76 [11.21, 19.13] | 14.15 [12.30, 20.44] | 0.495 |
STAT5A (median [IQR]) | 14.12 [10.23, 19.31] | 14.58 [11.02, 19.61] | 12.31 [9.28, 15.57] | 0.029 |
STAT5B (median [IQR]) | 16.90 [12.38, 21.67] | 17.59 [12.63, 22.01] | 14.92 [11.93, 18.83] | 0.069 |
The Expression Level of Genes (FPKM) | Total (N = 57) | FLT3 Wild-Type (N = 38) | FLT3 Mutant Group (N = 19) | p |
---|---|---|---|---|
FLT3 (median [IQR]) | 44.22 [26.32, 68.30] | 34.56 [20.98, 48.28] | 74.77 [54.31, 109.46] | <0.001 |
KRAS (median [IQR]) | 16.35 [13.13, 19.84] | 16.53 [13.46, 19.49] | 15.84 [12.70, 22.22] | 0.852 |
HRAS (median [IQR]) | 2.96 [2.43, 3.89] | 2.77 [2.11, 3.77] | 3.17 [2.82, 3.91] | 0.123 |
NRAS (median [IQR]) | 29.83 [24.84, 33.57] | 29.86 [25.28, 33.55] | 28.48 [23.02, 33.50] | 0.813 |
PIK3CA (median [IQR]) | 10.25 [8.22, 12.43] | 10.46 [9.22, 13.13] | 9.06 [7.32, 11.24] | 0.09 |
PIK3CB (median [IQR]) | 18.85 [14.46, 23.19] | 17.60 [13.28, 19.85] | 23.05 [18.81, 25.80] | 0.006 |
PIK3CD (median [IQR]) | 18.70 [15.47, 24.77] | 18.50 [15.39, 24.73] | 19.53 [16.52, 25.39] | 0.813 |
PIK3R3 (median [IQR]) | 0.26 [0.18, 0.57] | 0.26 [0.18, 0.66] | 0.26 [0.16, 0.44] | 0.542 |
AKT1 (median [IQR]) | 8.32 [6.19, 10.41] | 7.40 [5.55, 8.88] | 9.66 [8.38, 11.61] | 0.003 |
AKT2 (median [IQR]) | 7.31 [5.61, 8.81] | 7.32 [5.57, 8.72] | 7.28 [6.35, 8.82] | 0.531 |
AKT3 (median [IQR]) | 1.66 [1.00, 4.42] | 1.52 [1.01, 3.34] | 2.50 [1.00, 5.00] | 0.379 |
MTOR (median [IQR]) | 8.02 [7.21, 9.56] | 7.70 [6.79, 8.65] | 9.33 [7.75, 11.35] | 0.006 |
CHUK (median [IQR]) | 7.63 [6.33, 9.19] | 7.62 [6.29, 8.80] | 7.82 [6.36, 9.82] | 0.542 |
IKBKB (median [IQR]) | 7.96 [6.63, 9.41] | 7.59 [6.39, 9.54] | 8.55 [7.81, 9.36] | 0.128 |
IKBKG (median [IQR]) | 0.72 [0.56, 0.88] | 0.71 [0.56, 0.87] | 0.76 [0.61, 0.91] | 0.488 |
BAD (median [IQR]) | 3.47 [2.58, 4.20] | 3.12 [2.44, 4.05] | 3.76 [2.90, 4.61] | 0.108 |
BRAF (median [IQR]) | 12.03 [10.37, 14.27] | 11.37 [9.61, 13.19] | 13.38 [11.63, 15.12] | 0.015 |
RAF1 (median [IQR]) | 18.03 [15.47, 20.86] | 17.99 [15.39, 20.16] | 18.44 [17.02, 21.18] | 0.623 |
MAP2K1 (median [IQR]) | 10.33 [7.56, 13.11] | 11.78 [7.00, 14.80] | 9.87 [8.22, 11.14] | 0.335 |
MAP2K2 (median [IQR]) | 9.76 [7.95, 11.72] | 9.30 [7.55, 11.59] | 10.04 [9.58, 11.68] | 0.123 |
MAPK1 (median [IQR]) | 13.25 [11.09, 16.73] | 12.72 [11.02, 14.92] | 14.84 [13.07, 17.90] | 0.029 |
MAPK3 (median [IQR]) | 6.65 [5.51, 7.69] | 6.95 [5.50, 7.99] | 6.19 [5.81, 7.25] | 0.416 |
STAT3 (median [IQR]) | 26.38 [22.24, 30.81] | 26.59 [22.31, 30.70] | 25.97 [22.98, 30.17] | 0.879 |
STAT5A (median [IQR]) | 28.60 [22.79, 34.60] | 29.87 [21.83, 35.70] | 26.04 [23.79, 30.46] | 0.509 |
STAT5B (median [IQR]) | 20.34 [17.39, 23.76] | 20.43 [17.92, 23.75] | 20.34 [17.29, 23.88] | 0.787 |
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Zhao, L.; Chen, H.; Lan, F.; Hao, J.; Zhang, W.; Li, Y.; Yin, Y.; Huang, M.; Wu, X. Distinct FLT3 Pathways Gene Expression Profiles in Pediatric De Novo Acute Lymphoblastic and Myeloid Leukemia with FLT3 Mutations: Implications for Targeted Therapy. Int. J. Mol. Sci. 2024, 25, 9581. https://doi.org/10.3390/ijms25179581
Zhao L, Chen H, Lan F, Hao J, Zhang W, Li Y, Yin Y, Huang M, Wu X. Distinct FLT3 Pathways Gene Expression Profiles in Pediatric De Novo Acute Lymphoblastic and Myeloid Leukemia with FLT3 Mutations: Implications for Targeted Therapy. International Journal of Molecular Sciences. 2024; 25(17):9581. https://doi.org/10.3390/ijms25179581
Chicago/Turabian StyleZhao, Lizhen, Hongbo Chen, Fengli Lan, Jinjin Hao, Wenzhi Zhang, Ying Li, Yuhong Yin, Minchun Huang, and Xiaoyan Wu. 2024. "Distinct FLT3 Pathways Gene Expression Profiles in Pediatric De Novo Acute Lymphoblastic and Myeloid Leukemia with FLT3 Mutations: Implications for Targeted Therapy" International Journal of Molecular Sciences 25, no. 17: 9581. https://doi.org/10.3390/ijms25179581