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Rob Pieters - One of the best experts on this subject based on the ideXlab platform.
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elevated s100a8 s100a9 expression causes glucocorticoid resistance in mll rearranged infant Acute Lymphoblastic Leukemia
Leukemia, 2012Co-Authors: J A P Spijkershagelstein, Rob Pieters, P Schneider, Esther Hulleman, J De Boer, Owen Williams, Ronald W StamAbstract:Elevated S100A8/S100A9 expression causes glucocorticoid resistance in MLL -rearranged infant Acute Lymphoblastic Leukemia
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characterization of a pediatric t cell Acute Lymphoblastic Leukemia patient with simultaneous lyl1 and lmo2 rearrangements
Haematologica, 2012Co-Authors: Irene Homminga, Maartje J Vuerhard, Jessica G C A M Buijsgladdines, Anton W Langerak, Rob Pieters, Jules P P MeijerinkAbstract:Translocation of the LYL1 oncogene are rare in T-cell Acute Lymphoblastic Leukemia, whereas the homologous TAL1 gene is rearranged in approximately 20% of patients. Previous gene-expression studies have identified an immature T-cell Acute Lymphoblastic Leukemia subgroup with high LYL1 expression in the absence of chromosomal aberrations. Molecular characterization of a t(7;19)(q34;p13) in a pediatric T-cell Acute Lymphoblastic Leukemia patient led to the identification of a translocation between the TRB@ and LYL1 loci. Similar to incidental T-cell Acute Lymphoblastic Leukemia cases with synergistic, double translocations affecting TAL1/2 and LMO1/2 oncogenes, this LYL1-translocated patient also had an LMO2 rearrangement pointing to oncogenic cooperation between LYL1 and LMO2. In hierarchical cluster analyses based on gene-expression data, this sample consistently clustered along with cases having TAL1 or LMO2 rearrangements. Therefore, LYL1-rearranged cases are not necessarily associated with immature T-cell development, despite high LYL1 levels, but elicit a TALLMO expression signature.
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prognostic significance of high level flt3 expression in mll rearranged infant Acute Lymphoblastic Leukemia
Blood, 2007Co-Authors: Ronald W Stam, P Schneider, Paola De Lorenzo, Maria Grazia Valsecchi, Monique Den L Boer, Rob PietersAbstract:To the editor: Recently, we have demonstrated that in primary MLL -rearranged infant Acute Lymphoblastic Leukemia (ALL) samples, high-level expression of wild-type FLT3 is associated with FLT3 phosphorylation (ie, constitutive activation) and sensitivity toward the small-molecule FLT3 inhibitor
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silencing of the tumor suppressor gene fhit is highly characteristic for mll gene rearranged infant Acute Lymphoblastic Leukemia
Leukemia, 2006Co-Authors: Ronald W Stam, M Den L Boer, Monique Passier, G E Jankaschaub, Stephen E Sallan, Scott A Armstrong, Rob PietersAbstract:Silencing of the tumor suppressor gene FHIT is highly characteristic for MLL gene rearranged infant Acute Lymphoblastic Leukemia
Ronald W Stam - One of the best experts on this subject based on the ideXlab platform.
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elevated s100a8 s100a9 expression causes glucocorticoid resistance in mll rearranged infant Acute Lymphoblastic Leukemia
Leukemia, 2012Co-Authors: J A P Spijkershagelstein, Rob Pieters, P Schneider, Esther Hulleman, J De Boer, Owen Williams, Ronald W StamAbstract:Elevated S100A8/S100A9 expression causes glucocorticoid resistance in MLL -rearranged infant Acute Lymphoblastic Leukemia
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prognostic significance of high level flt3 expression in mll rearranged infant Acute Lymphoblastic Leukemia
Blood, 2007Co-Authors: Ronald W Stam, P Schneider, Paola De Lorenzo, Maria Grazia Valsecchi, Monique Den L Boer, Rob PietersAbstract:To the editor: Recently, we have demonstrated that in primary MLL -rearranged infant Acute Lymphoblastic Leukemia (ALL) samples, high-level expression of wild-type FLT3 is associated with FLT3 phosphorylation (ie, constitutive activation) and sensitivity toward the small-molecule FLT3 inhibitor
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silencing of the tumor suppressor gene fhit is highly characteristic for mll gene rearranged infant Acute Lymphoblastic Leukemia
Leukemia, 2006Co-Authors: Ronald W Stam, M Den L Boer, Monique Passier, G E Jankaschaub, Stephen E Sallan, Scott A Armstrong, Rob PietersAbstract:Silencing of the tumor suppressor gene FHIT is highly characteristic for MLL gene rearranged infant Acute Lymphoblastic Leukemia
Stephen E Sallan - One of the best experts on this subject based on the ideXlab platform.
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clinical course and outcome in children with Acute Lymphoblastic Leukemia and asparaginase associated pancreatitis
Pediatric Blood & Cancer, 2009Co-Authors: Susan Kearney, Stephen E Sallan, Donna E Levy, Suzanne E Dahlberg, Stephan D Voss, Lewis B SilvermanAbstract:Background Asparaginase, an agent used in the treatment of Acute Lymphoblastic Leukemia (ALL), is associated with the development of pancreatitis. The clinical course and long-term outcome of patients experiencing this complication has not been extensively detailed.
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silencing of the tumor suppressor gene fhit is highly characteristic for mll gene rearranged infant Acute Lymphoblastic Leukemia
Leukemia, 2006Co-Authors: Ronald W Stam, M Den L Boer, Monique Passier, G E Jankaschaub, Stephen E Sallan, Scott A Armstrong, Rob PietersAbstract:Silencing of the tumor suppressor gene FHIT is highly characteristic for MLL gene rearranged infant Acute Lymphoblastic Leukemia
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childhood t cell Acute Lymphoblastic Leukemia the dana farber cancer institute Acute Lymphoblastic Leukemia consortium experience
Journal of Clinical Oncology, 2003Co-Authors: John M Goldberg, Stephen E Sallan, Lewis B Silverman, Donna E Levy, Virginia Dalton, Richard D Gelber, Leslie E Lehmann, Harvey J Cohen, Barbara L AsselinAbstract:Purpose: T-cell Acute Lymphoblastic Leukemia (T-ALL) accounts for 10% to 15% of newly diagnosed cases of childhood Acute Lymphoblastic Leukemia (ALL). Historically, T-ALL patients have had a worse prognosis than other ALL patients. Patients and Methods: We reviewed the outcomes of 125 patients with T-ALL treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium trials between 1981 and 1995. Therapy included four- or five-agent remission induction; consolidation therapy with doxorubicin, vincristine, corticosteroid, mercaptopurine, and weekly high-dose asparaginase; and cranial radiation. T-ALL patients were treated the same as high-risk B-progenitor ALL patients. Fifteen patients with T-cell Lymphoblastic lymphoma were also treated with the same high-risk regimen between 1981 and 2000. Results: The 5-year event-free survival (EFS) rate for T-ALL patients was 75% ± 4%. Fourteen of 15 patients with T-cell Lymphoblastic lymphoma were long-term survivors. There was no significant difference in EFS compari...
Marina Konopleva - One of the best experts on this subject based on the ideXlab platform.
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cd123 expression patterns and selective targeting with a cd123 targeted antibody drug conjugate imgn632 in Acute Lymphoblastic Leukemia
Haematologica, 2019Co-Authors: Evgeniya Angelova, Charlene Audette, Yelena Kovtun, Naval Daver, Sa A Wang, Sherry Pierce, Sergej Konoplev, Haitham Khogeer, Jeffrey L Jorgensen, Marina KonoplevaAbstract:The potential of CD123-targeted therapies in Acute Lymphoblastic Leukemia/lymphoma remains largely unexplored. We examined CD123 expression levels in a large cohort of patients with Acute Lymphoblastic Leukemia/lymphoma and assessed the in vitro impact of IMGN632, a conjugate of CD123-binding antibody with a novel DNA-alkylating payload. CD123 expression on leukemic blasts was surveyed using multicolor/multiparameter flow cytometry. The in vitro effect of IMGN632 was evaluated on B Acute Lymphoblastic Leukemia/lymphoma cell lines and primary B Acute Lymphoblastic Leukemia/lymphoma blasts. The study cohort (n=213) included 183 patients with B Acute Lymphoblastic Leukemia/lymphoma and 30 with T Acute Lymphoblastic Leukemia/lymphoma. CD123 expression was more prevalent in B Acute Lymphoblastic Leukemia/lymphoma than in T Acute Lymphoblastic Leukemia/lymphoma (164/183, 89.6% versus 13/30, 43.3%; P<0.0001), and within B Acute Lymphoblastic Leukemia/lymphoma CD123 expression was more prevalent in Philadelphia chromosome-positive patients than in Philadelphia chromosome-negative patients (96.6% versus 86.3%; P=0.033). In T Acute Lymphoblastic Leukemia/lymphoma, 12/13 (92.3%) patients with CD123-positive blasts had either early T precursor (ETP) or early non-ETP immunophenotype. IMGN632 was highly cytotoxic to B Acute Lymphoblastic Leukemia/lymphoma cell lines, with half maximal inhibitory concentrations (IC50) between 0.6 and 20 pM. In five of eight patients' samples, low picomolar concentrations of IMGN632 eliminated more than 90% of the B Acute Lymphoblastic Leukemia/lymphoma blast population, sparing normal lymphocytes. In conclusion, CD123 expression is prevalent across Acute Lymphoblastic Leukemia/lymphoma subtypes, and the CD123-targeted antibody-drug conjugate IMGN632 demonstrates promising selective activity in preclinical models of B Acute Lymphoblastic Leukemia/lymphoma.
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cd123 expression patterns and selective targeting with a cd123 targeted antibody drug conjugate imgn632 in Acute Lymphoblastic Leukemia
Haematologica, 2019Co-Authors: Evgeniya A Angelova, Charlene Audette, Yelena Kovtun, Naval Daver, Sa A Wang, Sherry Pierce, Sergej Konoplev, Haitham Khogeer, Jeffrey L Jorgensen, Marina KonoplevaAbstract:The potential of CD123-targeted therapies in Acute Lymphoblastic Leukemia/lymphoma remains largely unexplored. We examined CD123 expression levels in a large cohort of patients with Acute Lymphoblastic Leukemia/lymphoma and assessed the in vitro impact of IMGN632, a conjugate of CD123-binding antibody with a novel DNA-alkylating payload. CD123 expression on leukemic blasts was surveyed using multicolor/multiparameter flow cytometry. The in vitro effect of IMGN632 was evaluated on B Acute Lymphoblastic Leukemia/lymphoma cell lines and primary B Acute Lymphoblastic Leukemia/lymphoma blasts. The study cohort (n=213) included 183 patients with B Acute Lymphoblastic Leukemia/lymphoma and 30 with T Acute Lymphoblastic Leukemia/lymphoma. CD123 expression was more prevalent in B Acute Lymphoblastic Leukemia/lymphoma than in T Acute Lymphoblastic Leukemia/lymphoma (164/183, 89.6% versus 13/30, 43.3%; P
Chinghon Pui - One of the best experts on this subject based on the ideXlab platform.
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brain network connectivity and executive function in long term survivors of childhood Acute Lymphoblastic Leukemia
Brain connectivity, 2018Co-Authors: Shelli R Kesler, Chinghon Pui, Robert J Ogg, Wilburn E Reddick, Nicholas S Phillips, Matthew A Scoggins, John O Glass, Yin Ting Cheung, Leslie L Robison, Melissa M HudsonAbstract:Abstract Chemotherapeutic agents used to treat Acute Lymphoblastic Leukemia (ALL), the most common cancer affecting young children, have been associated with long-term cognitive impairments that re...
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minimal residual disease guided therapy in childhood Acute Lymphoblastic Leukemia
Blood, 2017Co-Authors: Dario Campana, Chinghon PuiAbstract:### Case 1 A 3-year-old boy presented with a leukocyte count of 5.9 × 109/L and was found to have near-haploid B-lineage Acute Lymphoblastic Leukemia (ALL) with a 27, X, +Y, +13, +18, +21 karyotype. He was enrolled in the St. Jude Children’s Research Hospital Total Therapy XV study. After 19
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asparaginase may influence dexamethasone pharmacokinetics in Acute Lymphoblastic Leukemia
Journal of Clinical Oncology, 2008Co-Authors: Lei Yang, Chinghon Pui, Cheng Cheng, John C Panetta, Xiangjun Cai, Wenjian Yang, Deqing Pei, Nancy Kornegay, Mary V RellingAbstract:Purpose Dexamethasone is used widely in oncology, but pharmacokinetic studies are lacking. We evaluated dexamethasone pharmacokinetics in children with Acute Lymphoblastic Leukemia. Patients and Methods We assessed 214 children with Acute Lymphoblastic Leukemia who received 418 courses of oral dexamethasone (8 mg/m2/d) on days 1 and 8 of reinduction. Extensive asparaginase use preceded reinduction in the 101 children in the standard/high-risk treatment arm but not in the 113 children in the low-risk treatment arm. A one-compartment model with first-order absorption and disposition was fit to dexamethasone plasma concentrations by using maximum a posteriori probability estimation; we evaluated covariates by using linear mixed models. Results Interpatient and intrapatient variabilities in apparent clearance were substantial; they were 46% and 53%, respectively. Variability was explained by the serum albumin concentration (P < .0001), concomitant use of fentanyl (P = .008) and ketoconazole (P = .03), and age...
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are children with lesser risk b lineage Acute Lymphoblastic Leukemia curable with antimetabolite therapy
Nature Reviews Clinical Oncology, 2008Co-Authors: Chinghon Pui, William E Evans, Mary V RellingAbstract:Are children with lesser-risk B-lineage Acute Lymphoblastic Leukemia curable with antimetabolite therapy?
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treatment of Acute Lymphoblastic Leukemia
The New England Journal of Medicine, 2006Co-Authors: Chinghon Pui, William E EvansAbstract:Although the overall cure rate of Acute Lymphoblastic Leukemia (ALL) in children is about 80 percent, affected adults fare less well. This review considers recent advances in the treatment of ALL, emphasizing issues that need to be addressed if treatment outcome is to improve further.