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, Yuan; Xu, Lei; Yr, Liu; Yz, Qin; Sun, Yuanyuan; Wang, Y; Jiang, Hao; Jiang, Qian; Chen, H; Yj, Chang; Huang, Xiao‐Jun

doi:10.1038/bmt.2014.274

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…In our study, 15 patients in a group of 80 patients with Ph(+) ALL after allo-hematopoietic stem cell transplantation had CD34 + CD38 − lymphoblasts in the first immunophenotypic examination. The authors showed that three months after bone marrow transplantation, an increase in the BCR/ABL transcript was observed in this group of 15 patients, which correlated with a high 3-year cumulative incidence of relapse and worse leukemia-free survival and overall survival ( 30 ). Similar conclusions are presented by Shram et al ( 31 ).…”

Section: Discussionmentioning

confidence: 94%

Can CD34+CD38− lymphoblasts, as likely leukemia stem cells, be a prognostic factor in B-cell precursor acute lymphoblastic leukemia in children?

Stolpa,

Mizia-Malarz,

Zapała

et al. 2023

Front. Pediatr.

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BackgroundCD34+CD38− lymphoblasts as likely leukemia stem cells (LSCs) may be responsible for a worse response to treatment and may be a risk factor for recurrence in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).ObjectiveThe study objective was to assess the prognostic role of CD34+CD38− lymphoblasts in bone marrow on the day of BCP-ALL diagnosis.Methods115 patients with BCP-ALL, the median age of 4.5 years (range 1.5–17.9 years), gender: female 63 (54.8%) with BCP-ALL were enrolled; Group I (n = 90)—patients with CD34+CD38+ antigens and Group II (n = 20)—patients with CD34+CD38− antigens on the lymphoblast surface.ResultsA worse response on Days 8, 15, and 33 of therapy and at the end of treatment in Group II (CD34+CD38−) was more often observed but these differences were not statistically significant. A significantly higher incidence of BCP-ALL recurrence was in Group II.Conclusions1.In BCP-ALL in children, the presence of CD34+CD38− lymphoblasts at the diagnosis does not affect the first remission.2.In BCP-ALL in children, the presence of CD34+CD38− lymphoblasts at the diagnosis may be considered an unfavorable prognostic factor for disease recurrence.3.It is necessary to further search for prognostic factors in BCP-ALL in children.

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Section: Discussionmentioning

confidence: 94%

Can CD34+CD38− lymphoblasts, as likely leukemia stem cells, be a prognostic factor in B-cell precursor acute lymphoblastic leukemia in children?

Stolpa,

Mizia-Malarz,

Zapała

et al. 2023

Front. Pediatr.

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“…We found inferior outcome and poor prognosis in the CD34+CD38−CD58− group compared with that in the other phenotype groups. In addition Kong et al [ 16 ] found that in a cohort of patients with allogenic bone marrow transplantation, the presence of CD34+CD38−CD58− LPCs correlated directly with higher 3-year cumulative incidence of relapse, and worse leukemia free-survival and OS.…”

Section: Discussionmentioning

confidence: 99%

Leukemia propagating cells in Philadelphia chromosome-positive ALL: a resistant phenotype with an adverse prognosis

et al. 2018

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BackgroundTargeted therapy has revolutionized the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); however, relapse still occurs because of the presence of quiescent stem cells, termed leukemia propagating cells (LPCs). This study aimed to assess the phenotypic diversity of LPCs in adult patients with Ph+ B-Acute ALL (B-ALL) and to assess its prognostic impact.MethodsSeventy adults with newly diagnosed Ph+ B-ALL were recruited at the Mansoura Oncology Center. Multiparameter flow cytometry studies of mononuclear blast cells for cluster of differentiation (CD)34, CD38, and CD58 were performed.ResultsSeventeen patients had blasts with the pattern of LPCs (CD34+CD38−CD58−), while 53 cases had other diverse phenotypic patterns. The rate of complete response was significantly lower in patients with the LPC phenotype (47% vs. 81%, P=0.006). The median time to achieve a complete response was prolonged in patients with the CD34+CD38−CD58− phenotype (48 vs. 32 days, P=0.016). The three-year overall survival was significantly lower in patients with the CD34+CD38−CD58− phenotype (37% vs. 55% respectively, P=0.028). Multivariate analysis showed that the CD34+CD38− CD58− phenotype was an independent risk factor for overall survival.ConclusionThe presence of CD34+CD38−CD58− LPCs at diagnosis allows rapid identification of higher risk patients. Risk stratification of these patients is needed to further guide therapy and develop effective LPCs-targeted therapy to improve treatment outcome.

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“…In line with these data, more recently, several papers reported that relapse of Philadephia chromosome positive ALL (Ph + ALL) patients is due to the persistence of leukemia-initiating cells (LICs), a self-renewing CD34 + CD38 − CD58 − population, capable of initiating human leukemia in immune-deficient mice (94–97). Higher LICs frequencies at diagnosis are predictive of unfavorable prognosis and clinical outcome in AML (98–100) and are considered an independent risk factor for relapse (101). This holds true also in childhood ALL, where a high proportion of CD34 + CD38 − cells negatively correlates with disease outcome and represents a useful marker for patients' risk stratification (102).…”

Section: Expression and Functional Role Of Ectonucleotidases In Hematmentioning

confidence: 99%

Ectonucleotidases in Blood Malignancies: A Tale of Surface Markers and Therapeutic Targets

et al. 2019

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Leukemia develops as the result of intrinsic features of the transformed cell, such as gene mutations and derived oncogenic signaling, and extrinsic factors, such as a tumor-friendly, immunosuppressed microenvironment, predominantly in the lymph nodes and the bone marrow. There, high extracellular levels of nucleotides, mainly NAD+ and ATP, are catabolized by different ectonucleotidases, which can be divided in two families according to substrate specificity: on one side those that metabolize NAD+, including CD38, CD157, and CD203a; on the other, those that convert ATP, namely CD39 (and other ENTPDases) and CD73. They generate products that modulate intracellular calcium levels and that activate purinergic receptors. They can also converge on adenosine generation with profound effects, both on leukemic cells, enhancing chemoresistance and homing, and on non-malignant immune cells, polarizing them toward tolerance. This review will first provide an overview of ectonucleotidases expression within the immune system, in physiological and pathological conditions. We will then focus on different hematological malignancies, discussing their role as disease markers and possibly pathogenic agents. Lastly, we will describe current efforts aimed at therapeutic targeting of this family of enzymes.

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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

Cited by 6 publications

References 39 publications

Can CD34+CD38− lymphoblasts, as likely leukemia stem cells, be a prognostic factor in B-cell precursor acute lymphoblastic leukemia in children?

Can CD34+CD38− lymphoblasts, as likely leukemia stem cells, be a prognostic factor in B-cell precursor acute lymphoblastic leukemia in children?

Leukemia propagating cells in Philadelphia chromosome-positive ALL: a resistant phenotype with an adverse prognosis

Ectonucleotidases in Blood Malignancies: A Tale of Surface Markers and Therapeutic Targets

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