Abstract
BackgroundAlthough contemporary chemotherapy has improved the cure rate of childhood acute lymphoblastic leukemia (ALL) to nearly 90%, relapsed/refractory ALL is still a leading cause of tumor-related death in children. To clarify the underlying mechanisms of relapsed/refractory childhood ALL, researchers urgently need to establish novel cell models from patients with relapsed ALL after treatment with contemporary chemotherapy.MethodsCell culture technique was used to establish the HXEX-ALL1 cell line from primary B cell precursor ALL (BCP-ALL) cells. Molecular and cellular biological techniques including flow cytometry, polymerase chain reaction (PCR), short tandem repeat (STR) analysis, conventional cytogenetics, and chromosomal microarray analysis (CMA) were used to characterize the HXEX-ALL1 cell line. Nude mice were used for xenograft studies.ResultsA stable ALL cell line, HXEX-ALL1, derived from a 6-year-old boy of Han nationality with BCP-ALL at the second relapse, was established and maintained in culture for more than 18 months. The HXEX-ALL1 cell line was authenticated as being derived from primary leukemia cells based on morphologic, immunophenotypic, cytogenetic and STR analyses and demonstrated tumorigenicity in nude mice. WGS data showed that there were 27,006 novel single nucleotide polymorphisms (SNPs) and 193,951 novel insertion/deletions (InDels) in HXEX-ALL1 cells. Compared with the other BCP-ALL cell lines in use, the HXEX-ALL1 cells have a special karyotype represented by trisomy 8 and 9p and 17p deletions with a multidrug resistance phenotype, especially highly resistant to asparaginase.ConclusionsThe HXEX-ALL1 cell line may prove to be a useful model for the study of relapsed/refractory childhood ALL, particularly for the researches on asparaginase resistance.
Highlights
Contemporary chemotherapy has improved the cure rate of childhood acute lymphoblastic leukemia (ALL) to nearly 90%, relapsed/refractory ALL is still a leading cause of tumor-related death in children
The cells could be frozen under standard conditions using 60% RPMI-1640 medium, 30% fetal bovine serum (FBS) and 10% dimethyl sulfoxide (DMSO) and successfully revived after storage in liquid nitrogen, with more than 80% viability
Compared with the other B cell precursor ALL (BCP-ALL) cell lines in use [20, 21], the HXEX-ALL1 cells have a special karyotype represented by trisomy 8 and 9p and 17p deletions and display a multidrug resistant phenotype with highly resistant to L-Asp
Summary
Contemporary chemotherapy has improved the cure rate of childhood acute lymphoblastic leukemia (ALL) to nearly 90%, relapsed/refractory ALL is still a leading cause of tumor-related death in children. To clarify the underlying mechanisms of relapsed/refractory childhood ALL, researchers urgently need to establish novel cell models from patients with relapsed ALL after treatment with contemporary chemotherapy. In 1955, the first human leukemia cell line was derived from a patient with acute myeloid leukemia (AML) by Osgood and Burke [6]. This cell line soon became contaminated with HeLa cells [7]. The Raji cell line was established as the first leukemia-lymphoma cell line in 1963 by Pulvertaft [8]. There are no pediatric leukemia cell lines from China in the ATCC and DSMZ cell banks
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