Abstract

Rubinstein-Taybi syndrome (RSTS) is a rare disorder characterized by developmental delay, short stature, dysmorphic facies and skeletal abnormalities. RSTS has been linked to a variety of malignant and benign tumors, but the frequency and characteristics of RSTS-related neoplasms remain unclear. We describe a unique case of near haploid B-cell lymphoblastic leukemia (B-ALL) in a 6-year-old girl with RSTS who harbors a likely pathogenic variant in CREBBP. Somatic CREBBP variants are enriched in some subsets of ALL; however, germline variants have not been previously described in childhood leukemia and may represent an underrecognized predisposition to malignancy. Our patient’s disease responded poorly to conventional chemotherapy and relapsed following a complete remission achieved with CD19 CAR T cell therapy. We propose that the constitutional CREBBP variant may have played a significant role in the leukemia’s resistance to chemotherapy and this patient’s poor response to therapy.

摘要

Rubinstein-Taybi 综合征 (RSTS) 是一种罕见的疾病，其特征是发育迟缓、身材矮小、畸形面容和骨骼异常。RSTS 与多种恶性和良性肿瘤有关，但 RSTS 相关肿瘤的频率和特征仍不清楚。我们描述了一个独特的近单倍体 B 细胞淋巴细胞白血病 (B-ALL) 病例，该病例发生在一名 6 岁的 RSTS 女孩身上，该女孩在CREBBP中具有可能的致病性变异。体细胞CREBBP变异在 ALL 的某些子集中富集；然而，生殖系变异以前没有在儿童白血病中被描述过，并且可能代表了一种未被充分认识的恶性肿瘤易感性。我们的患者的疾病对常规化疗反应不佳，并且在通过 CD19 CAR T 细胞治疗实现完全缓解后复发。我们提出，构成性CREBBP变体可能在白血病对化疗的抗性和该患者对治疗的不良反应中发挥了重要作用。