Changes in endogenous TPO levels during mobilization chemotherapy are predictive of CD34+ megakaryocyte progenitor yield and identify patients at risk of delayed platelet engraftment post-PBPC transplant

Maharaj, Dipnarine; Steinberg, JP; Gouvea, J. V.; Gieser, PW

doi:10.1038/sj.bmt.1701618

Cited by 9 publications

(7 citation statements)

References 18 publications

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“…The CD34 þ CD61 þ subsets are regarded as MK progenitors and CD34ÀCD61 þ are the major characteristics of megakaryocytes. [25][26][27] Our results showed that, on day 6, the ratio of CD34ÀCD61 þ /CD34 þ CD61 þ cells is 4.07 in miR-181a-HPCs versus 1.96 in control HPCs, which implies that miR-181a may promote the development of MK progenitors (CD34 þ CD61 þ ) to megakaryocytes (CD34ÀCD61 þ ) instead of initiating MK differentiation, as shown in Table 1.…”

Section: Resultsmentioning

confidence: 84%

Erratum: MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit

Li¹,

Zhang²,

Gao³

et al. 2012

Cell Death Differ

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MicroRNAs (miRNAs) have attracted attention because of their key regulatory functions in many biological events, including differentiation and tumorigenesis. Recent studies have reported the existence of a reciprocal regulatory loop between the family of let-7 miRNAs and an RNA-binding protein, Lin28, both of which have been documented for their important roles during cell differentiation. Hence, using bipotent K562 human leukemia cells and human CD34 þ hematopoietic progenitor cells as research models, we demonstrate that let-7 and Lin28 have contrary roles in megakaryocytic (MK) differentiation with a dynamic balance; expression of miR-181 is capable of effectively repressing Lin28 expression, disrupting the Lin28-let-7 reciprocal regulatory loop, upregulating let-7, and eventually promoting MK differentiation. However, miR-181 lacks a significant effect on hemin-induced erythrocyte differentiation. These results demonstrate that miR-181 can function as a 'molecular switch' during hematopoietic lineage progression specific to MK differentiation, thus providing insight into future development of miRNA-oriented therapeutics.

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Section: Resultsmentioning

confidence: 84%

Erratum: MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit

Li¹,

Zhang²,

Gao³

et al. 2012

Cell Death Differ

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“…Similarly, the number of CD34 þ CD61 þ cells has not proved useful clinically in predicting slow platelet engraftment. 1,14 When we analysed expression of CD41/CD61 in conjunction with CD34 and CD110, we could not identify a more accurate method of predicting platelet engraftment based on expression of more mature platelet markers.…”

Section: Discussionmentioning

confidence: 99%

Failure to achieve a threshold dose of CD34+CD110+ progenitor cells in the graft predicts delayed platelet engraftment after autologous stem cell transplantation

Sartor

Garvin

Antonenas

et al. 2007

Bone Marrow Transplant

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In this study, we retrospectively analysed the utility of CD110 expression on CD34 þ cells as a predictor of delayed platelet transfusion independence in 39 patients who underwent autologous peripheral blood stem cell transplantation. Absolute CD34 þ cells and CD34 þ subsets expressing CD110 were enumerated using flow cytometry. Of the 39 patients, 7 required 21 days or more to achieve platelet transfusion independence. Six of the seven patients received a dose of CD34 þ CD110 þ cells below 6.0 Â 10 4 /kg while 30 of 32 patients who achieved platelet transfusion independence in o21 days received a dose of CD34 þ CD110 þ cells 46.0 Â 10 4 /kg (Po0.001). Patients with delayed platelet engraftment received a median dose of 5.2 Â 10 4 CD34 þ CD110 þ cells/kg compared with a median dose of 16.4 Â 10 4 cells/kg for those engrafting within 21 days (P ¼ 0.003). Further analysis showed that 46.0 Â 10 4 CD34 þ CD110 þ cells/ kg was highly sensitive (93.8%) and highly specific (85.7%) for achieving platelet transfusion independence within 21 days. Delay in platelet transfusion independence translated into an increased requirement for platelet transfusion (median 6 vs 2 transfusions, Po0.0001). The dose of CD34 þ /CD110 þ cells/kg infused at time of transplantation appears to be an important factor identifying patients at risk of delayed platelet engraftment.

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“…In the attempt to identify the group of patients at risk for prolonged thrombocytopenia, several reports have studied a series of autografts with the aim of evaluating the effect of CD34 + lineage-specific subset numbers on time to platelet engraftment. The most significant correlation was recognized for the CD34/CD61 + megakaryocytic cell [11,53,[58][59][60][61][62]. Furthermore, in analysis of uncommitted progenitors, Baech, Johnsen 78 we discovered an inverse correlation between the CD34/CD38or CD34/CD33subset and platelet engraftment, indicating that high numbers of CD34/CD38cells, i.e., early uncommitted progenitors, may increase the risk of delayed engraftment [11,52,53,[58][59][60][61][62][63][64][65][66][67][68][69].…”

Section: The Challenge Of Cd34 + Subset Analysismentioning

confidence: 99%

Technical Aspects and Clinical Impact of Hematopoietic Progenitor Subset Quantification

Bæch

Johnsen

2000

STEM CELLS

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As high-dose therapy for malignancies is now being applied to newly diagnosed patients as adjuvant therapy, it has become a requirement that quality and safety assessment of hematopoietic stem cell grafts be evidence-based. This process has developed a new institution in medicine, the stem cell laboratory. In most cases this speciality has evolved from or within hematological research laboratories. However, the increased routine technologies applied in quality evaluation, ex vivo manipulation and safety assessment in stem cell handling naturally places this activity in transfusion medicine.Multiparametric flow cytometry can identify progenitor subsets in normal human bone marrow and peripheral blood, and such subset quantification has been used retrospectively to predict three-lineage engraftment following high-dose therapy for malignancies. Published single center data have suggested an impact on clinical outcome, and a standardized technique for subset enumeration needs to be established before prospective multicenter trials can be initiated to document the prognostic value of such quality assessment in autografting.Based on experiences of CD34 enumeration, which we consider to be the first step in quality assessment of hematopoietic stem cell grafts, this review discusses flow cytometry subset identification by lineage-specific differentiation markers, stromal-dependent adherence molecules, and regulatory growth factor receptors from a technical point of view. The aim of this review is:• To recommend a simple method based on the experiences of the Nordic workshop III on subset identification;• To present new molecular genetic-based methods for future use in quality assessment; and• To propose new endpoints necessary for validation of the likely clinical impact of subsets in prospective trials.As sample differences between blood and marrow result in technical difficulties, this review only focuses on the methodology of identifying subsets in blood and leukapheresis products. Methods for subset analysis in diagnostic bone marrow samples will be covered in a forthcoming review.

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Changes in endogenous TPO levels during mobilization chemotherapy are predictive of CD34+ megakaryocyte progenitor yield and identify patients at risk of delayed platelet engraftment post-PBPC transplant

Cited by 9 publications

References 18 publications

Erratum: MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit

Erratum: MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit

Failure to achieve a threshold dose of CD34+CD110+ progenitor cells in the graft predicts delayed platelet engraftment after autologous stem cell transplantation

Technical Aspects and Clinical Impact of Hematopoietic Progenitor Subset Quantification

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