Citations 2
Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance)
Walker, Alison R. , Marcucci, Guido , Yin, Jun , Blum, William , Kohlschmidt, Jessica, Mrózek, Krzysztof , Carroll, Andrew J. , Eisfeld, Ann-Kathrin, Kolitz, Jonathan E. , Thakuri, Mohan C., Sutamtewagul, Grerk , Vij, Ravi , Byrd, John C. , Bloomfield, Clara D. , Stone, Richard M. , Byrd, John C. , Jacobson, Sawyer , Sutamtewagul, Grerk , Larson, Richard A , Stock, Wendy , Eisfeld, Ann‐Kathrin , Wang, Eunice S. , Stuart, Robert K. , Larson, Richard A. , Byrd, John C
Blood Advances | July 12, 2021 | Volume: 5 | Issue: 13 | Pages: 2775-2787
10.1182/bloodadvances.2021004233
Abstract Overexpression of B-cell leukemia/lymphoma 2 (BCL2) renders acute myeloid leukemia (AML) cells resistant to chemotherapy and has been associated with unfavorable outcomes. Oblimersen (G3139) is a phosphorothioate 18-mer antisense oligonucleotide directed against the first 6 BCL2 codons. In a phase 1 study of AML patients treated with G3139, cytarabine, and daunorubicin induction with cytarabine consolidation, no antisense-related toxicity was reported, and BCL2 downregulation occurred in patients achieving complete remission. In this phase 3 trial, untreated older AML patients were randomized to cytarabine (100 mg/m2 per day on days 4-10) and daunorubicin (60 mg/m2 per day on days 4-6) followed by cytarabine consolidation (2000 mg/m2 per day on days 4-8) with (arm A) or without (arm B) G3139 (7 mg/m2 per day on days 1-10 [induction] or days 1-8 [consolidation]). A total of 506 patients were enrolled. No differences in toxicity were observed between arms. Estimated overall survival (OS) at 1 year was 43% for arm A and 40% for arm B (1-sided log rank P = .13), with no differences in disease-free (DFS; P = .26) or event-free survival (P = .80). Subgroup analyses showed patients age <70 years in arm A had improved OS by 1 month vs those in arm B (P = .04), and patients with secondary AML in arm A had better DFS vs those in arm B (P = .04). We conclude that addition of G3139 to chemotherapy failed to improve outcomes of older AML patients. However, more effective means of inhibiting BCL2 are showing promising results in combination with chemotherapy in AML. This trial was registered at www.clinicaltrials.gov as #NCT00085124.
Expression and prognostic impact of lncRNAs in acute myeloid leukemia
Garzon, Ramiro , Volinia, Stefano , Papaioannou, Dimitrios , Kohlschmidt, Jessica, Yan, Pearlly S. , Mrózek, Krzysztof , Bucci, Donna, Carroll, Andrew J. , Baer, Maria R. , Wetzler, Meir , Carter, Thomas H. , Powell, Bayard L., Kolitz, Jonathan E. , Moore, Joseph O., Eisfeld, Ann-Kathrin, Blachly, James S. , Blum, William , Stone, Richard M. , Marcucci, Guido , Byrd, John C. , Bloomfield, Clara D. , Byrd, John C. , Nicolet, Deedra , Eisfeld, Ann‐Kathrin , Caligiuri, Michael A. , Croce, Carlo Maria , Blachly, James , Byrd, John C
Proceedings of the National Academy of Sciences | December 15, 2014 | Volume: 111 | Issue: 52 | Pages: 18679-18684
Significance Long noncoding RNAs (lncRNAs) are involved in numerous biological roles including epigenetic regulation, apoptosis, and cell cycle. Whereas lncRNAs contribute to epigenetic gene regulation, metastasis, and prognosis in solid tumors, their role in acute myeloid leukemia (AML) has not been hitherto reported. Here, we show that lncRNA expression profiles are associated with recurrent mutations, clinical features, and outcome in AML. A fraction of these lncRNAs may have a functional role in leukemogenesis. Furthermore, lncRNAs could be used as biomarkers for outcome in AML. The identification of patients likely to achieve complete remission with standard therapy alone, based on lncRNA expression, is a significant advance potentially sparing such patients from other toxicities and focusing investigational approaches on postremission studies.