Browsing by Author "Croop, James M."

Now showing 1 - 5 of 5
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    Evidence for BCR/ABL1‐positive T‐cell acute lymphoblastic leukemia arising in an early lymphoid progenitor cell
    (Wiley, 2019-09) Ragg, Susanne; Zehentner, Barbara K.; Loken, Michael R.; Croop, James M.; Pediatrics, School of Medicine
    BCR‐ABL1‐positive leukemias have historically been classified as either chronic myelogenous leukemia or Ph+ acute lymphoblastic leukemia. Recent analyses suggest there may be a wider range of subtypes. We report a patient with BCR‐ABL1 fusion positive T‐cell ALL with a previously undescribed cell distribution of the fusion gene. The examination of sorted cells by fluorescence in situ hybridization showed the BCR‐ABL1 fusion in the malignant T cells and a subpopulation of the nonmalignant B cells, but not nonmalignant T cells or myeloid or CD34+ progenitor cells providing evidence that the fusion may have occurred in an early lymphoid progenitor.
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    Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial
    (Elsevier, 2012-12) Robertson, Kent A.; Nalepa, Grzegorz; Yang, Feng-Chun; Bowers, Daniel C.; Ho, Chang Y.; Hutchins, Gary D.; Croop, James M.; Vik, Terry A.; Denne, Scott C.; Parada, Luis F.; Hingtgen, Cynthia M.; Walsh, Laurence E.; Yu, Menggang; Pradhan, Kamnesh R.; Edwards-Brown, Mary K.; Cohen, Mervyn D.; Fletcher, James W.; Travers, Jeffrey B.; Staser, Karl W.; Lee, Melissa W.; Sherman, Marcie R.; Davis, Cynthia J.; Miller, Lucy C.; Ingram, David A.; Clapp, D. Wade; Pediatrics, School of Medicine
    BACKGROUND: Plexiform neurofibromas are slow-growing chemoradiotherapy-resistant tumours arising in patients with neurofibromatosis type 1 (NF1). Currently, there are no viable therapeutic options for patients with plexiform neurofibromas that cannot be surgically removed because of their proximity to vital body structures. We undertook an open-label phase 2 trial to test whether treatment with imatinib mesylate can decrease the volume burden of clinically significant plexiform neurofibromas in patients with NF1. METHODS: Eligible patients had to be aged 3-65 years, and to have NF1 and a clinically significant plexiform neurofibroma. Patients were treated with daily oral imatinib mesylate at 220 mg/m(2) twice a day for children and 400 mg twice a day for adults for 6 months. The primary endpoint was a 20% or more reduction in plexiform size by sequential volumetric MRI imaging. Clinical data were analysed on an intention-to-treat basis; a secondary analysis was also done for those patients able to take imatinib mesylate for 6 months. This trial is registered with ClinicalTrials.gov, number NCT01673009. FINDINGS: Six of 36 patients (17%, 95% CI 6-33), enrolled on an intention-to-treat basis, had an objective response to imatinib mesylate, with a 20% or more decrease in tumour volume. Of the 23 patients who received imatinib mesylate for at least 6 months, six (26%, 95% CI 10-48) had a 20% or more decrease in volume of one or more plexiform tumours. The most common adverse events were skin rash (five patients) and oedema with weight gain (six). More serious adverse events included reversible grade 3 neutropenia (two), grade 4 hyperglycaemia (one), and grade 4 increases in aminotransferase concentrations (one). INTERPRETATION: Imatinib mesylate could be used to treat plexiform neurofibromas in patients with NF1. A multi-institutional clinical trial is warranted to confirm these results.
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    Parents' Insights into Pediatric Oncology Phase I Clinical Trials: Experiences from Their Child's Participation
    (Elsevier, 2021) Crane, Stacey; Croop, James M.; Lee, Jill; Walski, Jamie; Haase, Joan; School of Nursing
    Objectives: Phase 1 clinical trials are essential in the development of novel therapies for childhood cancers. Children with cancer can participate in phase 1 clinical trials when no known curative therapy remains. Understanding the experiences of children and their families in these clinical trials can help ensure that participation supports the children's and parents' well-being. This article explores the specific aspects of pediatric oncology phase 1 trials that parents found particularly challenging. Data sources: This qualitative, empirical phenomenology study considered 11 parents' experiences during the time their child with cancer participated in a phase 1 clinical trial. The primary study results were previously reported. This article reports parents' insights into the processes and procedures that occurred as part of participation in a pediatric oncology phase 1 trial. Conclusion: Parents' experiences during the phase 1 clinical trials were primarily positive. However, data analysis revealed five aspects of these trials that were challenging for families: learning about clinical trials, being referred to another institution, research-only procedures, adhering to trial requirements, and oral medications. Implications for nursing practice: Although experiences during phase 1 clinical trials were positive overall, opportunities to enhance children's and parents' experiences warrant attention. Enhancing the education provided to families during recruitment and minimizing the logistical burdens associated with trial requirements through care coordination may alleviate challenges experienced by children and parents.
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    PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371
    (American Society of Hematology, 2023) Chen, Hongxia; Bai, Yunpeng; Kobayashi, Michihiro; Xiao, Shiyu; Cai, Wenjie; Barajas, Sergio; Chen, Sisi; Miao, Jinmin; Nguele Meke, Frederick; Vemula, Sasidhar; Ropa, James P.; Croop, James M.; Boswell, H. Scott; Wan, Jun; Jia, Yuzhi; Liu, Huiping; Li, Loretta S.; Altman, Jessica K.; Eklund, Elizabeth A.; Ji, Peng; Tong, Wei; Band, Hamid; Huang, Danny T.; Platanias, Leonidas C.; Zhang, Zhong-Yin; Liu, Yan; Pediatrics, School of Medicine
    Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown. We discovered that genetic and pharmacological inhibition of PRL2 significantly reduce the burden of FLT3-internal tandem duplications-driven leukemia and extend the survival of leukemic mice. Furthermore, we found that PRL2 enhances oncogenic FLT3 signaling in leukemia cells, promoting their proliferation and survival. Mechanistically, PRL2 dephosphorylates the E3 ubiquitin ligase CBL at tyrosine 371 and attenuates CBL-mediated ubiquitination and degradation of FLT3, leading to enhanced FLT3 signaling in leukemia cells. Thus, our study reveals that PRL2 enhances oncogenic FLT3 signaling in leukemia cells through dephosphorylation of CBL and will likely establish PRL2 as a novel druggable target for AML.
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    PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation
    (American Association for Cancer Research, 2024) Chen, Hongxia; Bai, Yunpeng; Kobayashi, Michihiro; Xiao, Shiyu; Barajas, Sergio; Cai, Wenjie; Chen, Sisi; Miao, Jinmin; Meke, Frederick Nguele; Yao, Chonghua; Yang, Yuxia; Strube, Katherine; Satchivi, Odelia; Sun, Jianmin; Rönnstrand, Lars; Croop, James M.; Boswell, H. Scott; Jia, Yuzhi; Liu, Huiping; Li, Loretta S.; Altman, Jessica K.; Eklund, Elizabeth A.; Sukhanova, Madina; Ji, Peng; Tong, Wei; Band, Hamid; Huang, Danny T.; Platanias, Leonidas C.; Zhang, Zhong-Yin; Liu, Yan; Pediatrics, School of Medicine
    Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells. Implications: Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.