HLA-Matched and HLA-Haploidentical Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia with t (16;21) (p11.2;q22)

Yumiko Inui, Keiji Matsui, Hisayuki Matsumoto, Taku Nose, Rio Shiraki, Yuji Nakamachi, Katsuya Yamamoto, Atsuo Okamura
2020 Journal of Hematopoietic Cell Transplantation  
t 16;21 p11;q22 is a rare non-random chromosomal abnormality found in approximately 1% of acute myelogenous leukemia AML cases. 1 This chromosomal rearrangement results in FUS-ERG fusion transcripts. ERG, located at chromosome 21q22, is a member of the ets oncogene family. 2 Correct ERG gene dosage is critical to maintain hematopoietic stem cell function. FUS, at chromosome 16p11, encodes an RNA-binding protein with extensive amino-acid sequence homology to EWS, which is derived from Ewing
more » ... ved from Ewing sarcoma. 3 The FUS-ERG gene is produced by fusion of the 5 end of FUS to the 3 end of ERG. 4 The FUS fusion domain regulates DNA-binding activity of the FUS-ERG chimeric protein, resulting in weaker transcriptional activation than that with normal ERG proteins. 5 Dysregulation of normal ERG transcription by FUS-ERG fusion might contribute to the pathogenesis of AML with t 16;21 p11;q22 . AML with t 16;21 p11;q22 occurs more often in younger individuals for reasons not fully understood. Buchanan et al. compiled 78 cases and reported that the median age was 25 years. 6 AML with t 16;21 p11;q22 has Acute myelogenous leukemia(AML)with t(16;21) (p11;q22)is a rare leukemia subtype with a relatively high incidence in young individuals and a poor prognosis. This chromosomal rearrangement results in FUS-ERG fusion transcripts. We describe a patient with AML with t(16;21) (p11;q22)who underwent successful monitoring for FUS-ERG fusion transcripts by real-time quantitative polymerase chain reaction(RT-qPCR) . We designed DNA primers based on the leukemic cells of this patient and monitored minimal residual disease by RT-qPCR. Standard multiagent chemotherapy for AML could not reduce FUS-ERG expression level to 10 3 , whereas hematopoietic stem cell transplantation(HSCT)knocked down the expression level to 10 or lower. The patient underwent HSCT twice, and FUS-ERG expression decreased rapidly, especially after human leukocyte antigen(HLA)haploidentical HSCT. Although the patient suffered multiple early recurrences after HSCTs, this case suggests that HLA-haploidentical HSCT is one of the options for AML with t (16;21) (p11;q22) , even though the benefits are limited. Further research is needed to optimize the course of treatment including pre-transplant treatment, HSCT, and post-transplant treatment strategies(Trial registration:
doi:10.7889/hct-19-017 fatcat:imbmsorgmfbmbj5wb6kmain5iq