CD34+CD38−CD58− cells are leukemia-propagating cells in Philadelphia chromosome-positive acute lymphoblastic leukemia

Kong, Yuan; Yj, Chang; Yr, Liu; Yz, Wang; Jiang, Qian; Jiang, Hao; Yz, Qin; Hu, Youjin; Yy, Lai; Cw, Duan; Hong, Dengli; Huang, Xiao‐Jun

doi:10.1038/leu.2014.228

Cited by 13 publications

(22 citation statements)

References 14 publications

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“…3 However, challenges remain in implementing the experimentally validated biomarkers for recurrence prediction for risk-stratification therapy in Ph + ALL after allo-HSCT. In agreement with our previous report for de novoPh + ALL, 13 the novel CD34 + CD38 − CD58 − LPC phenotype has significant power to identify patients at high risk for relapse post HSCT. Although allo-HSCT exhibits the strongest anti-leukemia effects, it could not completely overcome the high risk of relapse in adult Ph + ALL patients with the candidate LPC phenotype.…”

Section: Discussionsupporting

confidence: 80%

“…16 Based on the blast phenotypes at diagnosis, subjects were further divided into the CD34 + CD38 − CD58 − group and other phenotype group (including subjects with CD34 + CD38 − CD58 + , CD34 + CD38 + CD58 − or CD34 + CD38 + CD58 + phenotypes and subjects with all of the above defined four fractions) as previously described. 13 Analyses were performed using MACSQuant software (Miltenyi Biotec).…”

Section: Materials and Methods Eligibilitymentioning

confidence: 99%

“…Three-year probabilities of LFS and OS were 68.51% (55-78.72%) and 72.34% (58.76-82.11%), respectively. Impact of the CD34 + CD38 − CD58 − LPC phenotype on clinical outcomes According to previously reported gating strategies, 13 the CD34 + CD38 − CD58 − LPC phenotype was detected in 15 subjects at diagnosis, whereas 65 subjects showed the other phenotype. As summarized in Table 1, the demographic and clinical characteristics showed no significant differences between the two phenotypic groups.…”

Section: Overall Outcomesmentioning

confidence: 99%

“…13 After two cycles of consolidation, subjects with a suitable donor, including a matched sibling donor, haploidentical donor or HLA-matched unrelated donor, received an allo-HSCT. The transplant protocols, including donor selection, HLA typing and stem cell harvesting, pre-transplant conditioning regimens and prophylaxis of GVHD, were conducted as described previously in detail.…”

Section: Treatment Protocolsmentioning

confidence: 99%

“…Moreover, our preliminary data indicate that a CD34 + CD38 − CD58 − LPC phenotype at diagnosis is an independent risk factor for relapse in a cohort of 63 patients with de novo Ph + ALL. 13 However, it is unclear if the reliability of the LPC phenotype to identify patients at high risk for relapse is relevant to Ph + ALL patients after allo-HSCT. Consequently, we conducted a cohort study to investigate the impact of the CD34 + CD38 − CD58 − LPC phenotype at diagnosis on allo-HSCT outcomes in 80 adults with Ph + ALL.…”

Section: Introductionmentioning

confidence: 99%

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Presence of CD34+CD38−CD58− leukemia-propagating cells at diagnosis identifies patients at high risk of relapse with Ph chromosome-positive ALL after allo-hematopoietic SCT

Kong

et al. 2014

Bone Marrow Transplant

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Relapse of Ph chromosome-positive ALL (Ph + ALL) results from the persistence of leukemia-propagating cells (LPCs). In Ph + ALL, a xenograft assay recently determined that LPCs are enriched in the CD34 + CD38 − CD58 − fraction. Therefore, the prognostic significance of LPCs in Ph + ALL subjects after allogeneic hematopoietic SCT (allo-HSCT) was investigated. A total of 80 consecutive adults with Ph + ALL who underwent allo-HSCT were eligible. A multi-parameter flow cytometry analysis examining CD58-FITC/ CD10-PE/ CD19-APC-Cy7/CD34-PerCP/CD45-Vioblue/ CD38-APC on gated leukemia BM blasts was performed at diagnosis. Based on the original blast phenotypes, subjects were stratified into the CD34 + CD38 − CD58 − group (N = 15) and other phenotype group (N = 65). During minimal residual disease monitoring, significantly higher levels of BCR/ABL transcripts were detected in subjects in the CD34 + CD38 − CD58 − group than in other phenotype group, especially at 3 months post HSCT. In addition, CD34 + CD38 − CD58 − LPCs are directly correlated with a higher 3-year cumulative incidence of relapse (CIR) and worse leukemia-free survival (LFS) and OS. Multivariate analyses indicated that presence of CD34 + CD38 − CD58 − LPCs at diagnosis, and BCR-ABL reduction at 3 months post HSCT were independent risk factors for relapse, LFS and OS. Our data suggest that presence of CD34 + CD38 − CD58 − LPCs at diagnosis allows rapid identification of high-risk patients for relapse after allo-HSCT.

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Section: Discussionsupporting

confidence: 80%

Section: Materials and Methods Eligibilitymentioning

confidence: 99%

Section: Overall Outcomesmentioning

confidence: 99%

Section: Treatment Protocolsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Presence of CD34+CD38−CD58− leukemia-propagating cells at diagnosis identifies patients at high risk of relapse with Ph chromosome-positive ALL after allo-hematopoietic SCT

Kong

et al. 2014

Bone Marrow Transplant

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Leukemic Stem Cells in Acute Lymphoblastic Leukemia

Testa

2015

Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology

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Leukemia-propagating cells demonstrate distinctive gene expression profiles compared with other cell fractions from patients with de novo Philadelphia chromosome-positive ALL

et al. 2018

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Relapse remains one of the major obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (PhALL) even after allogeneic hematopoietic stem cell transplantation. The persistence of leukemia-propagating cells (LPCs) may lead to the recurrence of PhALL. Using a xenograft assay, LPCs enrichment in the CD34CD38CD58 fraction in PhALL was recently identified. A further cohort study indicated that the LPCs phenotype at diagnosis was an independent risk factor for relapse of PhALL. However, little is known about the potential molecular mechanism of LPCs-mediated relapse. Therefore, the gene expression profiles of the sorted LPCs and other cell fractions from patients with de novo PhALL were investigated using RNA sequencing (RNA-Seq). Most of the differentially expressed genes between the LPCs and other cell fractions were related to the regulation of the cell cycle and metabolism, as identified by the gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Consistent with the RNA-Seq results, the mRNA levels of cell cycle-related genes, such as cyclin-dependent kinase 4, were significantly lower in the LPCs fraction than in other cell fractions. Moreover, the proportion of quiescent cells in LPCs was significantly higher than in other cell fractions. In summary, distinctive gene expression profiles and clusters, which were mostly related to the regulation of the cell cycle and metabolism, were demonstrated between LPCs and other cell fractions from patients with de novo PhALL. Therefore, it would be beneficial to develop novel LPCs-based therapeutic strategies for PhALL patients.

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CD34+CD38−CD58− cells are leukemia-propagating cells in Philadelphia chromosome-positive acute lymphoblastic leukemia

Cited by 13 publications

References 14 publications

Presence of CD34+CD38−CD58− leukemia-propagating cells at diagnosis identifies patients at high risk of relapse with Ph chromosome-positive ALL after allo-hematopoietic SCT

Presence of CD34+CD38−CD58− leukemia-propagating cells at diagnosis identifies patients at high risk of relapse with Ph chromosome-positive ALL after allo-hematopoietic SCT

Leukemic Stem Cells in Acute Lymphoblastic Leukemia

Leukemia-propagating cells demonstrate distinctive gene expression profiles compared with other cell fractions from patients with de novo Philadelphia chromosome-positive ALL

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