Abstract：Objective To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. Methods A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Results The ALL patients with CREBBP gene mutation accounted for 1.5% (14/963) among all children diagnosed with ALL during the same period of time, among whom there were 4 boys (29%) and 10 girls (71%), with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS, KRAS, ETV6, FLT3, PAX5, SH2B3, CDKN2A, and CDKN2B, and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen, with a complete remission (CR) rate of 79% (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone, with a recurrence rate of 21% (3/14), among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children, 1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92%±7%, and the event-free survival rate was 73%±13%. Conclusions ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate, and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.
Janczar S, Janczar K, Pastorczak A, et al. The role of histone protein modifications and mutations in histone modifiers in pediatric B-cell progenitor acute lymphoblastic leukemia[J]. Cancers (Basel), 2017, 9(1): 2. PMID: 28054944. PMCID: PMC5295773. DOI: 10.3390/cancers9010002.
Dixon ZA, Nicholson L, Zeppetzauer M, et al. CREBBP knockdown enhances RAS/RAF/MEK/ERK signaling in RAS pathway mutated acute lymphoblastic leukemia but does not modulate chemotherapeutic response[J]. Haematologica, 2017, 102(4): 736-745. PMID: 27979926. PMCID: PMC5395114. DOI: 10.3324/haematol.2016.145177.
Malinowska-Ozdowy K, Frech C, Sch?negger A, et al. KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia[J]. Leukemia, 2015, 29(8): 1656-1667. PMID: 25917266. PMCID: PMC4530204. DOI: 10.1038/leu.2015.107.
Paulsson K, Lilljebj?rn H, Biloglav A, et al. The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia[J]. Nat Genet, 2015, 47(6): 672-676. PMID: 25961940. DOI: 10.1038/ng.3301.
Inthal A, Zeitlhofer P, Zeginigg M, et al. CREBBP HAT domain mutations prevail in relapse cases of high hyperdiploid childhood acute lymphoblastic leukemia[J]. Leukemia, 2012, 26(8): 1797-1803. PMID: 22388726. PMCID: PMC4194312. DOI: 10.1038/leu.2012.60.
Tran TH, Hunger SP. The genomic landscape of pediatric acute lymphoblastic leukemia and precision medicine opportunities[J]. Semin Cancer Biol, 2022, 84: 144-152. PMID: 33197607. DOI: 10.1016/j.semcancer.2020.10.013.
Gao C, Liu SG, Lu WT, et al. Downregulating CREBBP inhibits proliferation and cell cycle progression and induces daunorubicin resistance in leukemia cells[J]. Mol Med Rep, 2020, 22(4): 2905-2915. PMID: 32945392. PMCID: PMC7453649. DOI: 10.3892/mmr.2020.11347.
