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14 results on '"Hunger, Stephen P"'

3. Outcomes in adolescent and young adult patients (16 to 30 years) compared to younger patients treated for high-risk B-lymphoblastic leukemia: report from Children’s Oncology Group Study AALL0232

Author

Burke, Michael J., Devidas, Meenakshi, Chen, Zhiguo, Salzer, Wanda L., Raetz, Elizabeth A., Rabin, Karen R., Heerema, Nyla A., Carroll, Andrew J., Gastier-Foster, Julie M., Borowitz, Michael J., Wood, Brent L., Winick, Naomi J., Carroll, William L., Hunger, Stephen P., Loh, Mignon L., and Larsen, Eric C.

Published
2022
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4. Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia

Author

Burns, Melissa A, Liao, Zi Wei, Yamagata, Natsuko, Pouliot, Gayle P, Stevenson, Kristen E, Neuberg, Donna S, Thorner, Aaron R, Ducar, Matthew, Silverman, Emily A, Hunger, Stephen P, Loh, Mignon L, Winter, Stuart S, Dunsmore, Kimberly P, Wood, Brent, Devidas, Meenakshi, Harris, Marian H, Silverman, Lewis B, Sallan, Stephen E, and Gutierrez, Alejandro

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Pediatric Cancer, Hematology, Genetics, Rare Diseases, Childhood Leukemia, Cancer, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Animals, Carcinogenesis, Cell Transformation, Neoplastic, Child, Child, Preschool, Female, Hedgehog Proteins, Humans, Male, Mutation, Oncogenes, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Signal Transduction, T-Lymphocytes, Zebrafish, Clinical Sciences, Immunology, Cardiovascular medicine and haematology, Clinical sciences, Oncology and carcinogenesis
Abstract

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease.

Published
2018

5. FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children’s Oncology Group trial AALL0631

Author

Brown, Patrick A., Kairalla, John A., Hilden, Joanne M., Dreyer, ZoAnn E., Carroll, Andrew J., Heerema, Nyla A., Wang, Cindy, Devidas, Meenakshi, Gore, Lia, Salzer, Wanda L., Winick, Naomi J., Carroll, William L., Raetz, Elizabeth A., Borowitz, Michael J., Small, Donald, Loh, Mignon L., and Hunger, Stephen P.

Published
2021
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8. Correction: Outstanding outcomes with two low intensity regimens in children with low-risk B-ALL: a report from COG AALL0932

Author

Schore, Reuven J., primary, Angiolillo, Anne L., additional, Kairalla, John A., additional, Devidas, Meenakshi, additional, Rabin, Karen R., additional, Zweidler-McKay, Patrick, additional, Borowitz, Michael J., additional, Wood, Brent, additional, Carroll, Andrew J., additional, Heerema, Nyla A., additional, Relling, Mary V., additional, Hitzler, Johann, additional, Kadan-Lottick, Nina S., additional, Maloney, Kelly, additional, Wang, Cindy, additional, Carroll, William L., additional, Winick, Naomi J., additional, Raetz, Elizabeth A., additional, Loh, Mignon L., additional, and Hunger, Stephen P., additional

Published
2023
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9. Flow-cytometric vs. -morphologic assessment of remission in childhood acute lymphoblastic leukemia: a report from the Children’s Oncology Group (COG)

Author

Gupta, Sumit, Devidas, Meenakshi, Loh, Mignon L., Raetz, Elizabeth A., Chen, Si, Wang, Cindy, Brown, Patrick, Carroll, Andrew J., Heerema, Nyla A., Gastier-Foster, Julie M., Dunsmore, Kimberly P., Larsen, Eric C., Maloney, Kelly W., Mattano, Jr., Leonard A., Winter, Stuart S., Winick, Naomi J., Carroll, William L., Hunger, Stephen P., Borowitz, Michael J., and Wood, Brent L.

Published
2018
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10. Correction to: FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children’s Oncology Group trial AALL0631

Author

Brown, Patrick A., Kairalla, John A., Hilden, Joanne M., Dreyer, ZoAnn E., Carroll, Andrew J., Heerema, Nyla A., Wang, Cindy, Devidas, Meenakshi, Gore, Lia, Salzer, Wanda L., Winick, Naomi J., Carroll, William L., Raetz, Elizabeth A., Borowitz, Michael J., Small, Donald, Loh, Mignon L., and Hunger, Stephen P.

Published
2021
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11. Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children’s Oncology Group study

Author

Rheingold, Susan R., Bhojwani, Deepa, Ji, Lingyun, Xu, Xinxin, Devidas, Meenakshi, Kairalla, John A., Shago, Mary, Heerema, Nyla A., Carroll, Andrew J., Breidenbach, Heather, Borowitz, Michael, Wood, Brent L., Angiolillo, Anne L., Asselin, Barbara L., Bowman, W. Paul, Brown, Patrick, Dreyer, ZoAnn E., Dunsmore, Kimberly P., Hilden, Joanne M., Larsen, Eric, Maloney, Kelly, Matloub, Yousif, Mattano, Leonard A., Winter, Stuart S., Gore, Lia, Winick, Naomi J., Carroll, William L., Hunger, Stephen P., Raetz, Elizabeth A., and Loh, Mignon L.

Abstract

Limited prognostic factors have been associated with overall survival (OS) post-relapse in childhood Acute Lymphoblastic Leukemia (ALL). Patients enrolled on 12 Children’s Oncology Group frontline ALL trials (1996–2014) were analyzed to assess for additional prognostic factors associated with OS post-relapse. Among 16,115 patients, 2053 (12.7%) relapsed. Relapse rates were similar for B-ALL (12.5%) and T-ALL (11.2%) while higher for infants (34.2%). Approximately 50% of B-ALL relapses occurred late (≥36 months) and 72.5% involved the marrow. Conversely, 64.8% of T-ALL relapses occurred early (<18 months) and 47.1% involved the central nervous system. The 5-year OS post-relapse for the entire cohort was 48.9 ± 1.2%; B-ALL:52.5 ± 1.3%, T-ALL:35.5 ± 3.3%, and infant ALL:21.5 ± 3.9%. OS varied by early, intermediate and late time-to-relapse; 25.8 ± 2.4%, 49.5 ± 2.2%, and 66.4 ± 1.8% respectively for B-ALL and 29.8 ± 3.9%, 33.3 ± 7.6%, 58 ± 9.8% for T-ALL. Patients with ETV6::RUNX1or Trisomy 4 + 10 had median time-to-relapse of 43 months and higher OS post-relapse 74.4 ± 3.1% and 70.2 ± 3.6%, respectively. Patients with hypodiploidy, KMT2A-rearrangement, and TCF3::PBX1had short median time-to-relapse (12.5-18 months) and poor OS post-relapse (14.2 ± 6.1%, 31.9 ± 7.7%, 36.8 ± 6.6%). Site-of-relapse varied by cytogenetic subtype. This large dataset provided the opportunity to identify risk factors for OS post-relapse to inform trial design and highlight populations with dismal outcomes post-relapse.

Published
2024
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12. Outstanding outcomes with two low intensity regimens in children with low-risk B-ALL: a report from COG AALL0932

Author

Schore, Reuven J., Angiolillo, Anne L., Kairalla, John A., Devidas, Meenakshi, Rabin, Karen R., Zweidler-McKay, Patrick, Borowitz, Michael J., Wood, Brent, Carroll, Andrew J., Heerema, Nyla A., Relling, Mary V., Hitzler, Johann, Kadan-Lottick, Nina S., Maloney, Kelly, Wang, Cindy, Carroll, William L., Winick, Naomi J., Raetz, Elizabeth A., Loh, Mignon L., and Hunger, Stephen P.

Published
2023
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13. Outcomes in adolescent and young adult patients (16 to 30 years) compared to younger patients treated for high-risk B-lymphoblastic leukemia: report from Children’s Oncology Group Study AALL0232

Author

Burke, Michael J., primary, Devidas, Meenakshi, additional, Chen, Zhiguo, additional, Salzer, Wanda L., additional, Raetz, Elizabeth A., additional, Rabin, Karen R., additional, Heerema, Nyla A., additional, Carroll, Andrew J., additional, Gastier-Foster, Julie M., additional, Borowitz, Michael J., additional, Wood, Brent L., additional, Winick, Naomi J., additional, Carroll, William L., additional, Hunger, Stephen P., additional, Loh, Mignon L., additional, and Larsen, Eric C., additional

Published
2021
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14. Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children’s Oncology Group Studies P9904 and P9905

Author

Winick, Naomi, primary, Martin, Paul L., additional, Devidas, Meenakshi, additional, Shuster, Jonathan, additional, Borowitz, Michael J., additional, Paul Bowman, W., additional, Larsen, Eric, additional, Pullen, Jeanette, additional, Carroll, Andrew, additional, Willman, Cheryl, additional, Hunger, Stephen P., additional, Carroll, William L., additional, and Camitta, Bruce M., additional

Published
2019
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