ASCT2-Targeting Antibody-Drug Conjugate MEDI7247 in Adult Patients with Relapsed/Refractory Hematological Malignancies: A First-in-Human, Phase 1 Study
ConclusionsThrombocytopenia and neutropenia limited repeat dosing. Although limited clinical activity was detected, the dose-escalation phase was stopped early without establishing an MTD.The study was registered with ClinicalTrials.gov (NCT03106428). (Source: Targeted Oncology)
Source: Targeted Oncology - April 29, 2024 Category: Cancer & Oncology Source Type: research
A higher CD34 + cell dose correlates with better event-free survival after KIR-ligand mismatched cord blood transplantation for childhood acute myeloid leukemia
Although killer Ig-like receptor ligands (KIR-L) mismatch has been associated with alloreactive natural killer cell activity and potent graft-versus-leukemia (GVL) effect among adults with acute myeloid leukem... (Source: Journal of Hematology and Oncology)
Source: Journal of Hematology and Oncology - April 29, 2024 Category: Hematology Authors: Hisashi Ishida, Yuta Kawahara, Daisuke Tomizawa, Yasuhiro Okamoto, Asahito Hama, Yuko Cho, Katsuyoshi Koh, Yuhki Koga, Nao Yoshida, Maho Sato, Kiminori Terui, Naoyuki Miyagawa, Akihiro Watanabe, Junko Takita, Ryoji Kobayashi, Masaki Yamamoto & hellip; Tags: Correspondence Source Type: research
ONC212 enhances YM155 cytotoxicity by triggering SLC35F2 expression and NOXA-dependent MCL1 degradation in acute myeloid leukemia cells
In this study, we investigated the apoptotic mechanism of ONC212 in acute myeloid leukemia (AML) cells. ONC212 induces apoptosis, MCL1 downregulation, and mitochondrial depolarization in AML U937 cells. Ectopic MCL1 expression alleviates mitochondria-mediated apoptosis in ONC212-treated U937 cells. ONC212 triggers AKT phosphorylation, inducing NOX4-dependent ROS production and promoting HuR transcription. HuR-mediated ATF4 mRNA stabilization stimulates NOXA and SLC35F2 expression; ONC212-induced upregulation of NOXA leads to MCL1 degradation. The synergistic effect of ONC212 on YM155 cytotoxicity was dependent on increased...
Source: Biochemical Pharmacology - April 28, 2024 Category: Drugs & Pharmacology Authors: Jing-Ting Chiou Long-Sen Chang Source Type: research
Proteomic Analysis Reveals Trilaciclib-Induced Senescence
Mol Cell Proteomics. 2024 Apr 26:100778. doi: 10.1016/j.mcpro.2024.100778. Online ahead of print.ABSTRACTTrilaciclib, a CDK4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer (ES-SCLC). This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in haematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in haematological cancers. Utilizing mass spectrometry-based prote...
Source: Molecular and Cellular Proteomics : MCP - April 28, 2024 Category: Molecular Biology Authors: Marina Hermosilla-Trespaderne Mark Xinchen Hu-Yang Abeer Dannoura Andrew M Frey Amy L George Matthias Trost Jos é Luis Marín-Rubio Source Type: research
ONC212 enhances YM155 cytotoxicity by triggering SLC35F2 expression and NOXA-dependent MCL1 degradation in acute myeloid leukemia cells
In this study, we investigated the apoptotic mechanism of ONC212 in acute myeloid leukemia (AML) cells. ONC212 induces apoptosis, MCL1 downregulation, and mitochondrial depolarization in AML U937 cells. Ectopic MCL1 expression alleviates mitochondria-mediated apoptosis in ONC212-treated U937 cells. ONC212 triggers AKT phosphorylation, inducing NOX4-dependent ROS production and promoting HuR transcription. HuR-mediated ATF4 mRNA stabilization stimulates NOXA and SLC35F2 expression; ONC212-induced upregulation of NOXA leads to MCL1 degradation. The synergistic effect of ONC212 on YM155 cytotoxicity was dependent on increased...
Source: Biochemical Pharmacology - April 28, 2024 Category: Drugs & Pharmacology Authors: Jing-Ting Chiou Long-Sen Chang Source Type: research
Proteomic Analysis Reveals Trilaciclib-Induced Senescence
Mol Cell Proteomics. 2024 Apr 26:100778. doi: 10.1016/j.mcpro.2024.100778. Online ahead of print.ABSTRACTTrilaciclib, a CDK4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer (ES-SCLC). This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in haematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in haematological cancers. Utilizing mass spectrometry-based prote...
Source: Molecular and Cellular Proteomics : MCP - April 28, 2024 Category: Molecular Biology Authors: Marina Hermosilla-Trespaderne Mark Xinchen Hu-Yang Abeer Dannoura Andrew M Frey Amy L George Matthias Trost Jos é Luis Marín-Rubio Source Type: research
Proteomic Analysis Reveals Trilaciclib-Induced Senescence
Mol Cell Proteomics. 2024 Apr 26:100778. doi: 10.1016/j.mcpro.2024.100778. Online ahead of print.ABSTRACTTrilaciclib, a CDK4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer (ES-SCLC). This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in haematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in haematological cancers. Utilizing mass spectrometry-based prote...
Source: Molecular and Cellular Proteomics : MCP - April 28, 2024 Category: Molecular Biology Authors: Marina Hermosilla-Trespaderne Mark Xinchen Hu-Yang Abeer Dannoura Andrew M Frey Amy L George Matthias Trost Jos é Luis Marín-Rubio Source Type: research
Proteomic Analysis Reveals Trilaciclib-Induced Senescence
Mol Cell Proteomics. 2024 Apr 26:100778. doi: 10.1016/j.mcpro.2024.100778. Online ahead of print.ABSTRACTTrilaciclib, a CDK4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer (ES-SCLC). This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in haematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in haematological cancers. Utilizing mass spectrometry-based prote...
Source: Molecular and Cellular Proteomics : MCP - April 28, 2024 Category: Molecular Biology Authors: Marina Hermosilla-Trespaderne Mark Xinchen Hu-Yang Abeer Dannoura Andrew M Frey Amy L George Matthias Trost Jos é Luis Marín-Rubio Source Type: research
Proteomic Analysis Reveals Trilaciclib-Induced Senescence
Mol Cell Proteomics. 2024 Apr 26:100778. doi: 10.1016/j.mcpro.2024.100778. Online ahead of print.ABSTRACTTrilaciclib, a CDK4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer (ES-SCLC). This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in haematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in haematological cancers. Utilizing mass spectrometry-based prote...
Source: Molecular and Cellular Proteomics : MCP - April 28, 2024 Category: Molecular Biology Authors: Marina Hermosilla-Trespaderne Mark Xinchen Hu-Yang Abeer Dannoura Andrew M Frey Amy L George Matthias Trost Jos é Luis Marín-Rubio Source Type: research
Acute mixed-lineage leukemia treated with desensitization therapy prior to HLA-haploidentical transplantation with high donor-specific antibodies
Int J Hematol. 2024 Apr 27. doi: 10.1007/s12185-024-03775-3. Online ahead of print.ABSTRACTA 43-year-old woman was referred to our department for hematopoietic stem cell transplantation for acute myeloid leukemia, as she failed to achieve remission following induction therapy. Umbilical cord blood transplantation was initially planned; however, multiple anti-human leukocyte antigen (HLA) antibodies with a mean fluorescence intensity of over 10,000 were detected, and optimal umbilical cord blood could not be obtained. The plan was then switched to peripheral blood stem cell transplantation (PBSCT) from the patient's son, wh...
Source: International Journal of Hematology - April 27, 2024 Category: Hematology Authors: Kengo Katsuki Takayoshi Tachibana Akihiko Izumi Kumryo Kim Taisei Suzuki Masatsugu Tanaka Hideaki Nakajima Source Type: research
Acute mixed-lineage leukemia treated with desensitization therapy prior to HLA-haploidentical transplantation with high donor-specific antibodies
Int J Hematol. 2024 Apr 27. doi: 10.1007/s12185-024-03775-3. Online ahead of print.ABSTRACTA 43-year-old woman was referred to our department for hematopoietic stem cell transplantation for acute myeloid leukemia, as she failed to achieve remission following induction therapy. Umbilical cord blood transplantation was initially planned; however, multiple anti-human leukocyte antigen (HLA) antibodies with a mean fluorescence intensity of over 10,000 were detected, and optimal umbilical cord blood could not be obtained. The plan was then switched to peripheral blood stem cell transplantation (PBSCT) from the patient's son, wh...
Source: International Journal of Hematology - April 27, 2024 Category: Hematology Authors: Kengo Katsuki Takayoshi Tachibana Akihiko Izumi Kumryo Kim Taisei Suzuki Masatsugu Tanaka Hideaki Nakajima Source Type: research
Acute mixed-lineage leukemia treated with desensitization therapy prior to HLA-haploidentical transplantation with high donor-specific antibodies
Int J Hematol. 2024 Apr 27. doi: 10.1007/s12185-024-03775-3. Online ahead of print.ABSTRACTA 43-year-old woman was referred to our department for hematopoietic stem cell transplantation for acute myeloid leukemia, as she failed to achieve remission following induction therapy. Umbilical cord blood transplantation was initially planned; however, multiple anti-human leukocyte antigen (HLA) antibodies with a mean fluorescence intensity of over 10,000 were detected, and optimal umbilical cord blood could not be obtained. The plan was then switched to peripheral blood stem cell transplantation (PBSCT) from the patient's son, wh...
Source: International Journal of Hematology - April 27, 2024 Category: Hematology Authors: Kengo Katsuki Takayoshi Tachibana Akihiko Izumi Kumryo Kim Taisei Suzuki Masatsugu Tanaka Hideaki Nakajima Source Type: research
Myelodysplastic Neoplasms (MDS): The Current and Future Treatment Landscape
Curr Oncol. 2024 Apr 3;31(4):1971-1993. doi: 10.3390/curroncol31040148.ABSTRACTMyelodysplastic neoplasms (MDS) are a heterogenous clonal disorder of hemopoietic stem cells characterized by cytomorphologic dysplasia, ineffective hematopoiesis, peripheral cytopenias and risk of progression to acute myeloid leukemia (AML). Our understanding of this disease has continued to evolve over the last century. More recently, prognostication and treatment have been determined by cytogenetic and molecular data. Specific genetic abnormalities, such as deletion of the long arm of chromosome 5 (del(5q)), TP53 inactivation and SF3B1 mutati...
Source: Current Oncology - April 26, 2024 Category: Cancer & Oncology Authors: Daniel Karel Claire Valburg Navitha Woddor Victor E Nava Anita Aggarwal Source Type: research
A comparative analysis of the clinical and genetic profiles of blast phase BCR::ABL1-negative myeloproliferative neoplasm and acute myeloid leukemia, myelodysplasia-related
CONCLUSION: MPN-BP and AML-MR harbor similar somatic mutations and clinical outcomes, suggesting a unified clinical disease entity.PMID:38665121 | DOI:10.1111/ijlh.14280 (Source: International Journal of Laboratory Hematology)
Source: International Journal of Laboratory Hematology - April 26, 2024 Category: Hematology Authors: Dong Chen Julia Geyer Adam Bagg Robert Hasserjian Olga K Weinberg Source Type: research
RNF138 inhibits transcription factor C/EBP α protein turnover leading to differentiation arrest in AML
Biochem J. 2024 Apr 26:BCJ20240027. doi: 10.1042/BCJ20240027. Online ahead of print.ABSTRACTE3 ubiquitin ligase, ring finger protein 138 (RNF138) is involved in several biological processes; however, its role in myeloid differentiation or tumorigenesis remains unclear. RNAseq data from TNMplot showed that RNF138 mRNA levels are highly elevated in Acute Myeloid Leukemia (AML) bone marrow samples as compared to bone marrow of normal volunteers. Here, we show that RNF138 serves as an E3 ligase for the tumor suppressor CCAAT/enhancer binding protein (C/EBPα) and promotes its degradation leading to myeloid differentiation arre...
Source: The Biochemical Journal - April 26, 2024 Category: Biochemistry Authors: Anil Kumar Singh Vishal Upadhyay Arppita Sethi Sangita Chaowdhury Shivkant Mishra Shailednra Prasad Verma Madan Lal Brahma Bhatt Arun Kumar Trivedi Source Type: research
