AUTHOR=Nishiwaki Satoshi , Kim Jeong Hui , Ito Masafumi , Maeda Matsuyoshi , Okuno Yusuke , Koyama Daisuke , Ozawa Yukiyasu , Gunji Masaharu , Osaki Masahide , Kitamura Kunio , Ushijima Yoko , Ishikawa Yuichi , Miyamura Koichi , Sugiura Isamu , Kiyoi Hitoshi 

TITLE=Multi-Lineage BCR-ABL Expression in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Associated With Improved Prognosis but No Specific Molecular Features

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.586567

DOI=10.3389/fonc.2020.586567

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Recently, various blood cell lineages expressing the <italic>BCR-ABL</italic> fusion gene in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have been reported. However, the biological and clinical significance of these <italic>BCR-ABL</italic> lineages has not been established; therefore, we aimed to clarify the impacts of these different <italic>BCR-ABL</italic>-expressing lineages.</p></sec><sec><title>Patients</title><p>Multi-lineage <italic>BCR-ABL</italic> expression (multi-Ph) was defined as <italic>BCR-ABL</italic> expression outside of the B-lineage compartment, as determined by fluorescence <italic>in situ</italic> hybridization (FISH) in peripheral blood neutrophils and bone marrow clots, and flow cytometry-sorted polymerase chain reaction (PCR). We analyzed <italic>IKZF1</italic> deletion patterns by PCR, examined gene expression profiles using RNA sequencing, and compared treatment outcomes across different <italic>BCR-ABL</italic>-expressing lineages.</p></sec><sec><title>Results</title><p>Among the 21 multi-Ph patients in our 59-patient cohort (36%), <italic>BCR-ABL</italic> expression was detected at the multipotential progenitor level. However, no <italic>IKZF1</italic> deletion patterns or gene expression profiles were identified that were specific for multi-Ph. However, multi-Ph patients were found to have better survival rates than patients with uni-lineage <italic>BCR-ABL</italic> expression [event-free survival (EFS): 74 vs. 33%, <italic>P</italic> = 0.01; overall survival (OS): 79 vs. 44% at 4 years, <italic>P</italic> = 0.01]. In multivariate analyses, multi-Ph was identified as a good prognostic factor for both EFS and OS.</p></sec><sec><title>Conclusion</title><p>We confirmed that more than one-third of Ph+ALL patients could be classified as mutli-Ph. Although no specific molecular characteristics were identified for multi-Ph, this phenotype was associated with better treatment outcomes.</p></sec>