Zhang Ge, Zhang Yanle, Wu Jianrong, Chen Yan, Ma Zhigui
Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China (mainland).
Am J Case Rep. 2017 Nov 14;18:1204-1208. doi: 10.12659/ajcr.906300.
BACKGROUND Chromosomal translocations involving the PDGFRB gene have been reported in a broad spectrum of hematological malignancies. An ATF7IP/PDGFRB fusion was recently identified in a Philadelphia chromosome-like (Ph-like) B-progenitor acute lymphoblastic leukemia (B-ALL) patient. Here we report on a special case of a Ph-like ALL patient who had a variant ATF7IP/PDGFRB fusion. CASE REPORT In this case, a variant fusion was created between ATF7IP exon 9 (instead of exon 13) and PDGFRB exon 11, resulting in the loss of 411 nucleotides and 137 amino acids in the ATF7IP/PDGFRB fusion cDNA and its encoded chimeric protein, respectively. Interestingly, ATF7IP has also been reported as a fusion partner of the JAK2 kinase gene in Ph-like ALL, but all of the genomic breakpoints in ATF7IP in this fusion reported thus far occurred in intron 13. Enforced expression of the variant ATF7IP/PDGFRB fusion induced cytokine-independent growth and glucocorticoid resistance of BaF3 cells. Similar to the initially described ATF7IP/PDGFRB-bearing Ph-like ALL patient who was refractory to conventional chemotherapy but highly sensitive to tyrosine kinase inhibitor (TKI) monotherapy, our patient with a variant ATF7IP/PDGFRB fusion had a poor initial treatment response to chemotherapy but responded well to TKI-based therapy and is now doing well in continuous remission. CONCLUSIONS Ph-like ALL patient with an ATF7IP/PDGFRB fusion is rare, but can benefit from TKI therapy.
涉及血小板衍生生长因子受体β（PDGFRB）基因的染色体易位已在多种血液系统恶性肿瘤中被报道。最近在一例费城染色体样（Ph样）B祖细胞急性淋巴细胞白血病（B-ALL）患者中鉴定出一种ATF7IP/PDGFRB融合基因。在此，我们报告一例特殊的Ph样ALL患者，其具有变异型ATF7IP/PDGFRB融合基因。病例报告：在该病例中，ATF7IP外显子9（而非外显子13）与PDGFRB外显子11之间形成了变异型融合，导致ATF7IP/PDGFRB融合cDNA及其编码的嵌合蛋白分别缺失411个核苷酸和137个氨基酸。有趣的是，ATF7IP也被报道为Ph样ALL中JAK2激酶基因的融合伴侣，但迄今为止报道的该融合中ATF7IP的所有基因组断点均发生在内含子13。变异型ATF7IP/PDGFRB融合基因的强制表达诱导了BaF3细胞的细胞因子非依赖性生长和糖皮质激素耐药性。与最初描述的携带ATF7IP/PDGFRB的Ph样ALL患者相似，该患者对传统化疗难治，但对酪氨酸激酶抑制剂（TKI）单药治疗高度敏感，我们这位具有变异型ATF7IP/PDGFRB融合基因的患者初始化疗反应不佳，但对基于TKI的治疗反应良好，目前处于持续缓解状态且情况良好。结论：具有ATF7IP/PDGFRB融合基因的Ph样ALL患者罕见，但可从TKI治疗中获益。
