Overlooked molecular machine in cell nucleus may hold key to treating aggressive leukemia

(Cincinnati Children's Hospital Medical Center) Many people fighting a very aggressive form of acute myeloid leukemia (AML) don't survive more than five years. These very sick patients are often unable to receive the only cure -- a bone marrow transplant. Now, an international team of scientists report in Nature Cell Biology on a long-overlooked part of a leukemic cell's internal machinery, where they may have found a key to treating the aggressive blood cancer.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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The era of next-generation sequencing (NGS) has led to a deeper understanding of the genetic complexity and heterogeneity of this disease, in addition to revealing mechanisms of disease relapse. Clinical NGS is becoming routine in clinical practice in both solid organ and hematologic malignancies to identify molecular markers of disease that might assist with diagnosis, prognosis, and the treatment of cancer. These tumor-specific markers also enable treatment response monitoring, as they serve as clonal markers unique to the disease. Continuous molecular monitoring also allows identification of disease recurrence with pote...
Source: Pathology Case Reviews - Category: Pathology Tags: Case Reviews Source Type: research
ConclusionWe confirmed that myeloablative Bu/Flu conditioning has comparable clinical and QOL outcomes to Bu/Cy.
Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
Despite improvements in supportive care and bone marrow transplantation, only 25% of patients diagnosed with Acute Myeloid Leukemia will survive beyond 5 years. While the emergence of targeted immunotherapy has opened new possibilities, clinical studies with chimeric antigen T-cells (CAR-T) cells have shown limited success beyond CD19-targeted immunotherapy, due to lack of unique targetable cell surface antigens and the possible management of B cell aplasia with immunoglobulin supplements. To be an ideal candidate for immunotherapy, an antigen should be unique to cancer cells, indispensable for their survival and not expre...
Source: Experimental Hematology - Category: Hematology Authors: Source Type: research
This article reviews data from several phase I、II clinical trials that evaluating PD-1 and CTLA-4 inhibitors on AML patients and discusses especially efficacy and adverse events as well as prospects of these drugs in treating acute myeloid leukemia.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions The discovery of JAK2V617F mutation in BCR-ABL1-negative MPNs by four different international cooperative groups in 2005 (2–5) led to significant insights on the pathogenesis of these disorders. In fact, this mutation results in a gain-of-function with activation of cytokine and growth factor receptors, and thus of the downstream JAK-STAT pathway (79, 95–98). The JAK2 point mutation in exon 12, present in a small percentage of patients with PV, is able to induce the MPN phenotype through the same pathogenic mechanism (6, 7). In 2006 the MPLW515L/K was reported in ET and PMF patients (44, 45) and d...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion This case demonstrates successful cure of pre-B-ALL complicating XLA by alloSCT with restoration of B-cell development and functional antibody response. We are aware of only one previous case of pre-B-ALL in an XLA patient (21), which suggests that human BTK deficiency in itself does not predispose to pre-B-ALL. However, there are data to suggest that BTK may act as a tumor suppressor, and BTK deficiency may predispose to tumor development following a “second hit.” Mice with a genetic deficiency in Slp65, a gene encoding an adaptor protein that functions together with BTK, have a block in progenito...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: This prospective multicenter study provides information on the current incidence and outcome of IFD in the real life setting. Practice variation between the centers may help to ultimately improve antifungal management in children at highest risk for IFDs. Introduction Available data on the incidence and outcome of invasive fungal diseases (IFD) in children treated for a hematological malignancy or undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are mostly based on single site, retrospective studies or on studies performed prior to the availability of newer compounds such as broad-sp...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
As Tyler Bacon gripped the lectern in Carnesale Commons and scanned the crowd gazing at him expectantly, he struggled to hold back tears.The 39-year-old father of two from Thousand Oaks was finally meeting some of the more than two dozen people whose blood and platelet donations sustained his life during cancer treatment at  Ronald Reagan UCLA Medical Center.  “Because you showed up and donated, my parents still have a son,” Bacon said. “My children have a dad. My wife has a husband.”His voice quaking with emotion, he added, “All the gratitude in the world would not be enough to say ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
As Tyler Bacon gripped the lectern in Carnesale Commons and scanned the crowd gazing at him expectantly, he struggled to hold back tears.The 39-year-old father of two from Thousand Oaks was finally meeting some of the more than two dozen people whose blood and platelet donations sustained his life during cancer treatment at  Ronald Reagan UCLA Medical Center.  “Because you showed up and donated, my parents still have a son,” Bacon said. “My children have a dad. My wife has a husband.”His voice quaking with emotion, he added, “All the gratitude in the world would not be enough to say ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
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