Interpretation of interleukin‐2 receptor alpha positive cells during induction chemotherapy for adult acute myelogenous leukaemia patients

Min, Woo-Sung; Kim, Hee-Je; Choi, Young Hoon; Jeong, Hye-Young; Kim, Chun-Choo

doi:10.1002/hon.807

Cited by 9 publications

(11 citation statements)

References 9 publications

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“…[12][13][14] Therefore, many recent clinical studies have relied on PBSCs as a cell source in such cases. Some conflicting results have been reported with respect to chronic GVHD before 2000, when we performed G-CSF-mobilized peripheral blood stem cell transplantation (PBSCT).…”

Section: Discussionmentioning

confidence: 99%

“…Chemotherapy before SCT Since its introduction in 1996, our center's chemotherapy regimen for AML has undergone several modifications that have been documented in previous publications, [12][13][14][15] and all patients enrolled in this study were treated according to the last updated standard protocol. All patients with AML were subjected to the same induction and consolidation strategy.…”

Section: Patientsmentioning

confidence: 99%

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Overcoming various comorbidities by G-CSF-primed unmanipulated BM SCT in adult patients with AML

Kim

et al. 2009

Bone Marrow Transplant

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We examined whether the use of G-CSF-primed unmanipulated bone marrow (pBM) permits successful transplantation in patients with adverse comorbid pretransplantation conditions. A total of 33 patients at variable risk of AML undergoing allogeneic SCT from an HLA-identical sibling participated. The patients suffered from a variety of treatment-related sequelae before SCT and many cases also featured the presence of major organ dysfunction. The median follow-up duration of patients who were among the overall survivors was 58 months (range, 11À125 months). The median number of CD34 þ cells infused was 3.5 Â 10 6 per kg (range, 0.8À15.6 Â 10 6 per kg). The median number of days for recovery of ANC and platelet count without transfusion was 13 (range, 6À22) and 18 (range, 11À29) days, respectively. Four patients (12%) died due to nonrelapse causes and only one patient developed the same course of infectious complication as before SCT. No particular finding in the context of CMV infection or other post transplant complication was observed. The estimated 10-year overall survival rate was 68%. Our results suggest that the use of pBM allows successful engraftment without increasing complications in patients with various comorbidities before transplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Overcoming various comorbidities by G-CSF-primed unmanipulated BM SCT in adult patients with AML

Kim

et al. 2009

Bone Marrow Transplant

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“…38 In addition, the evaluation of CD25-positive populations prior, during, and after induction chemotherapy showed that a majority of poorly responding patients demonstrated an increased percentage of CD25-positive cells at day 7 and day 21 after initiation of induction chemotherapy. 39 These clinical results suggest the possibility that chemotherapy may enhance the expression of CD25 in a subset of cells through activation of STAT5 activity and contribute to the subsequent relapse of disease. To determine whether this observation could be recapitulated in an in vitro system, we treated KG1 cells with sub-IC 50 doses of cytarabine and monitored CD25 mRNA expression levels (supplemental Figure 8).…”

Section: Identification Of Aml Cell Lines Sensitive To the Inhibitionmentioning

confidence: 93%

PIM inhibitors target CD25-positive AML cells through concomitant suppression of STAT5 activation and degradation of MYC oncogene

Guo

Wang

Zhang

et al. 2014

Blood

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Key Points• CD25 is a predictive biomarker for sensitivity to PIM inhibitors in AML cells.• PIM inhibitors may prolong overall/relapse-free survival through attenuating STAT5 activation and destabilizing MYC in CD25 1 AML cells.Postchemotherapy relapse presents a major unmet medical need in acute myeloid leukemia (AML), where treatment options are limited. CD25 is a leukemic stem cell marker and a conspicuous prognostic marker for overall/relapse-free survival in AML. Rare occurrence of genetic alterations among PIM family members imposes a substantial hurdle in formulating a compelling patient stratification strategy for the clinical development of selective PIM inhibitors in cancer. Here we show that CD25, a bona fide STAT5 regulated gene, is a mechanistically relevant predictive biomarker for sensitivity to PIM kinase inhibitors. Alone or in combination with tyrosine kinase inhibitors, PIM inhibitors can suppress STAT5 activation and significantly shorten the half-life of MYC to achieve substantial growth inhibition of high CD25-expressing AML cells. Our results highlight the importance of STAT5 and MYC in rendering cancer cells sensitive to PIM inhibitors. Because the presence of a CD25-positive subpopulation in leukemic blasts correlates with poor overall or relapse-free survival, our data suggest that a combination of PIM inhibitors with chemotherapy and tyrosine kinase inhibitors could improve long-term therapeutic outcomes in

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“…All patients were treated according to our center's standard protocol, which consists of 3 × 7 idarubicin (IDA) plus N4‐behenoyl‐1‐β‐D‐arabinofuranosyl cytosine (BH‐AC) induction chemotherapy, as described previously . All patients with non‐APL who achieved first CR received one ( n = 38) or two ( n = 83) more courses of consolidation chemotherapy with the standard regimen at our center.…”

Section: Methodsmentioning

confidence: 99%

Combinatorial molecular marker assays of WT1,survivin, and TERT at initial diagnosis of adult acute myeloid leukemia

Kim

Choi

Sohn

et al. 2013

European J of Haematology

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High levels of expression of Wilms' tumor gene 1 (WT1), survivin, or telomerase reverse transcriptase (TERT) genes are introduced as leukemia-associated targets predicting clinical outcome. We prospectively investigated the leukemia-associated gene transcripts by real-time quantitative polymerase chain reaction from 151 adult patients with AML associated with the patients' clinical characteristics. The maximum levels of each gene in bone marrow were 64.4-, 8.1-, and 3.9-fold higher than those in the normal control, respectively. In contrast to the WT1 and TERT levels, survivin showed comparatively higher expression in the unfavorable cytogenetic group of patients. We found a significant difference in survivin levels between the CR and non-CR groups (P = 0.0237). TERT expression levels were higher in patients who had a greater number of peripheral blood leukemic blasts at diagnosis (P = 0.0191). Non-MRC subtypes and patients without specific mutations were the most powerful predictive factors for a better CR rate, by multivariate analyses. The lower levels of both WT1 and survivin co-expression (P = 0.0129) and both survivin + TERT co-expression (P = 0.0115) were significant factors for better OS. Besides lower initial levels of serum ferritin (P = 0.0401), lower levels of WT1 (P = 0.0438) and survivin (P = 0.0401), lower levels of both WT1 and survivin co-expression (P = 0.0031), and the three-gene combination of lower WT1 + survivin + TERT (P = 0.0454) were powerful predictive factors for better EFS. As our findings were based on a single disease entity, that is, adult AML, they suggest that the expression of these genes may be critical for the immunobiology of AML to influence the clinical outcome in various ways.

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Interpretation of interleukin‐2 receptor alpha positive cells during induction chemotherapy for adult acute myelogenous leukaemia patients

Cited by 9 publications

References 9 publications

Overcoming various comorbidities by G-CSF-primed unmanipulated BM SCT in adult patients with AML

Overcoming various comorbidities by G-CSF-primed unmanipulated BM SCT in adult patients with AML

PIM inhibitors target CD25-positive AML cells through concomitant suppression of STAT5 activation and degradation of MYC oncogene

Combinatorial molecular marker assays of WT1,survivin, and TERT at initial diagnosis of adult acute myeloid leukemia

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