Julia T Warren, Daniel C Link
Clonal hematopoiesis is common in older persons and is associated with an increased risk of hematologic cancer. Here, we review studies establishing an association between clonal hematopoiesis and hematopoietic malignancy, discuss features of clonal hematopoiesis that are predictive of leukemic progression, and explore the role of hematopoietic stressors in the evolution of clonal hematopoiesis to acute myeloid leukemia or myelodysplastic syndrome. Clonal hematopoiesis due to point mutations or structural variants, such as copy number alterations, are associated with an approximately 10-fold increased risk of hematopoietic malignancy...
July 31, 2020: Blood
Kirby D Johnson, Daniel J Conn, Evgenia Shishkova, Koichi R Katsumura, Peng Liu, Siqi Shen, Erik A Ranheim, Sean G Kraus, Weixin Wang, Katherine R Calvo, Amy P Hsu, Steven M Holland, Joshua J Coon, Sunduz Keles, Emery H Bresnick
Stem and progenitor cell fate transitions constitute key decision points in organismal development that enable access to a developmental path or actively preclude others. Using the hematopoietic system, we analyzed the relative importance of cell fate-promoting mechanisms versus negating fate-suppressing mechanisms to engineer progenitor cells with multilineage differentiation potential. Deletion of the murine Gata2-77 enhancer, with a human equivalent that causes leukemia, downregulates the transcription factor GATA2 and blocks progenitor differentiation into erythrocytes, megakaryocytes, basophils, and granulocytes, but not macrophages...
November 2, 2020: Journal of Experimental Medicine
Frederick D Tsai, R Coleman Lindsley
Inherited bone marrow failure syndromes (IBMFS) are characterized by ineffective hematopoiesis and increased risk of developing myeloid malignancy. The pathophysiologies of different IBMFS are variable, and can relate to defects in diverse biological processes, including DNA damage repair (Fanconi anemia), telomere maintenance (dyskeratosis congenita), and ribosome biogenesis (Diamond-Blackfan anemia, Shwachman-Diamond syndrome). Somatic mutations leading to clonal hematopoiesis have been described in IBMFS, but the distinct mechanisms by which mutations drive clonal advantage in each disease and their associations with leukemia risk are not well understood...
July 31, 2020: Blood
Jeremy A Hengst, Shailaja Hegde, Robert F Paulson, Jong K Yun
Our sphingosine kinase inhibitor (SKI) optimization studies originated with the optimization of the SKI-I chemotype by replacement of the substituted benzyl rings with substituted phenyl rings giving rise to the discovery of SKI-178. We have recently reported that SKI-178 is a dual-targeted inhibitor of both sphingosine kinase isoforms (SphK1/2) and a microtubule disrupting agent (MDA). In mechanism-of-action studies, we have shown that these two separate actions synergize to induce cancer cell death in acute myeloid leukemia (AML) cell and animal models...
July 28, 2020: Bioorganic & Medicinal Chemistry Letters
Vasant Chinnabhandar, Steven Tran, Rosemary Sutton, Peter J Shaw, Francoise Mechinaud, Catherine Cole, Heather Tapp, Lochie Teague, Chris Fraser, Tracey A O'Brien, Richard Mitchell
Total body irradiation (TBI)/cyclophosphamide (CY) is a standard of care conditioning regimen in allogeneic hematopoietic stem cell transplant (HSCT) for pediatric acute lymphoblastic leukemia (ALL). This study sought to identify whether the addition of thiotepa (TT) to TBI/CY improves HSCT outcomes for pediatric patients with ALL. A retrospective analysis was performed on 347 pediatric ALL patients who underwent HSCT between 1995 and 2015, with 242 receiving TBI/CY/TT and 105 patients receiving TBI/CY. There were no statistical differences in age, donor source, or CR status between the two groups...
July 28, 2020: Biology of Blood and Marrow Transplantation
Eman O Rasekh, Ghada M Elsayed, Sherouk Fathy
BACKGROUND: Acute promyelocytic leukemia is a peculiar disease with few studies that have investigated the prognostic significance of PML/RARA transcript level at diagnosis. PATIENTS AND METHODS: This retrospective study included all cases diagnosed with acute promyelocytic leukemia over the period from June 2015 to March 2019. The normalized copy number (NCN) was tested by real-time polymerase chain reaction at diagnosis, and at the end of induction regimen. RESULTS: Our study included 83 de novo APL patients, 53 (63...
July 24, 2020: Hematology/oncology and Stem Cell Therapy
Amanda C Winters, Kelly W Maloney, Amy L Treece, Lia Gore, Anna K Franklin
BACKGROUND: The BCL-2 inhibitor venetoclax (ven) has revolutionized the treatment of acute myeloid leukemia (AML) in elderly adults, leading to its recent FDA approval for this population in combination regimens. Although extensive data exist for adult myeloid malignancies, there are limited preclinical data on the efficacy and/or dosing of venetoclax for pediatric myelodysplastic syndrome (MDS) or AML and thus little information to guide use of this regimen in pediatric patients. Our objective was to describe our single-center experience with venetoclax in combination with the hypomethylating agent 5-azacitidine (aza) in pediatric patients with MDS or AML...
July 31, 2020: Pediatric Blood & Cancer
Sunita K Patel, Christopher Johansen, Abigail Onderwyzer Gold, Nicole Delgado, Sandra Xu, Jessica Dennis
BACKGROUND: Children with brain tumor or acute leukemia are at risk for neurotoxic side effects associated with their cancer therapies. These long-term deficits include poor health-related quality of life (HRQOL) in school and lower educational achievement. Although social-ecological factors may impact these outcomes, it is not known which factors play a role. Our objective was to evaluate the factors affecting school HRQOL in Hispanic childhood cancer survivors, an important at-risk group...
July 31, 2020: Pediatric Blood & Cancer
Sunita K Patel, Leticia Miranda, Nicole Delgado, Nicolas Barreto, Anne Nolty, Natalie C Kelly, Karla Wilson, Debbie Toomey, Anna Pawlowska
OBJECTIVE: Survivors of childhood leukemia, especially those from low socioeconomic status households, often experience persistent neurocognitive and academic impairment. This study adapted an existing parent training intervention to improve outcomes for low-acculturated, Spanish-speaking Latino parents of children with leukemia and pilot tested that intervention for feasibility. METHODS: Semistructured interviews were conducted with a focus group of 20 Latino parents of children treated for leukemia...
July 31, 2020: Journal of Pediatric Psychology
Daniel Kristensen, Søren Niemi Helsø, Paw Jensen, Marianne Tang Severinsen, Anne Stidsholt Roug
This is a case report of a 68-year-old female referred to the SARS-CoV-2 ward with one week of intermittent fever and three days of progressive loss of vision. Laboratory work-up revealed severe coagulopathy, thrombocytopenia and hyperleukocytosis. MRI showed multiple ischaemic cortical lesions. Acute treatment with all-trans retinoic acid and cytoreduction was started and coagulation parameters corrected. Patients referred to pandemic wards must undergo stringent examination and be referred for further evaluation irrespective of suspected severe acute respiratory syndrome coronavirus-2 infection...
July 13, 2020: Ugeskrift for Laeger
Sanyukta K Janardan, Lyn M Balsamo, Wilhelmenia L Ross, Jaime Rotatori, Claudia Auerbach, Nina S Kadan-Lottick
PURPOSE: Adult childhood cancer survivors are frequently accompanied by a parent to survivorship clinic. From clinical evaluations among young adult survivors of childhood cancer we aimed to (1) investigate the association between accompaniment and the survivors' health complexity; and (2) determine whether accompaniment is associated with adherence to recommended surveillance tests and follow-up in clinic. METHODS: This was a cross-sectional study of all patients ≥ 18 years old at their first visit to the regional Yale Childhood Cancer Survivorship Clinic from 2003 to 2018...
July 31, 2020: Supportive Care in Cancer
Kazuhiro Saso, Norikatsu Miyoshi, Shiki Fujino, Masaru Sasaki, Masayoshi Yasui, Masayuki Ohue, Takayuki Ogino, Hidekazu Takahashi, Mamoru Uemura, Chu Matsuda, Tsunekazu Mizushima, Yuichiro Doki, Hidetoshi Eguchi
BACKGROUND: In recent years, systemic chemotherapy has significantly improved the prognosis of metastatic colorectal cancer (CRC); however, different patients have different responses to chemotherapeutics. METHODS: Dipeptidyl peptidase 9 (DPP9) is an enzyme in the dipeptidyl peptidase IV family that has been reported to increase drug sensitivity in acute myeloid leukemia. In this study, we examined the relationship between DPP9 expression and the prognosis of patients with CRC, as well as the role of DPP9 in anticancer drug resistance...
July 30, 2020: Annals of Surgical Oncology
Xia Xiao, Xiaoyuan He, Qing Li, Wei Zhang, Haibo Zhu, Weihong Yang, Yuming Li, Li Geng, Hui Liu, Lijuan Li, Huaquan Wang, Rong Fu, Mingfeng Zhao, Zhong Chen, Zonghong Shao
Background: Chromosomal abnormalities play an important role in the diagnosis and prognosis of patients with myelodysplastic syndromes (MDSs). The single-nucleotide polymorphism array (SNP-A) technique has gained popularity due to its improved resolution compared to that of metaphase cytogenetic (MC) analysis. Methods: A total of 376 individuals were recruited from two medical centers in China, including 350 patients and 26 healthy individuals. Among these patients, 200 were diagnosed with de novo MDS, 25 with myeloproliferative neoplasm (MPN), 63 with primary acute myeloid leukemia (AML), and 62 with idiopathic cytopenia of undetermined significance (ICUS)...
2020: Frontiers in Oncology
Mert Erciyestepe, Tarık Onur Tiryaki, İpek Yönal Hindilerden, Gülçin Yeğen, Meliha Nalçacı
Multiple myeloma is a type of plasma cell disorder and can be seen in different forms. According to current knowledge, it is not a curable disease. Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and distinguished from monoclonal gammopathy of undetermined significance by a much higher risk of progression to multiple myeloma. We present a 53-year-old female patient who started with SMM which turned into multiple myeloma after four years. Despite 26 cycles of lenalidomide treatment, we performed the second autologous stem transplantation...
2020: Case Reports in Hematology
Omar Castaneda Puglianini, Nikolaos Papadantonakis
Early precursor T cell-acute lymphoblastic leukemia (ETP-ALL) is a rare entity characterized by chemo-resistance and a paucity of data regarding optimal management. We review here the literature regarding the management of ETP-ALL and focus on the recent, emerging data, regarding the potential role of molecularly targeted approaches with a focus on venetoclax.
2020: Therapeutic Advances in Hematology
Stephan Klöß, Susann Dehmel, Armin Braun, Michael J Parnham, Ulrike Köhl, Susanne Schiffmann
Success in cancer treatment over the last four decades has ranged from improvements in classical drug therapy to immune oncology. Anti-cancer drugs have also often proven beneficial for the treatment of inflammatory and autoimmune diseases. In this review, we report on challenging examples that bridge between treatment of cancer and immune-mediated diseases, addressing mechanisms and experimental models as well as clinical investigations. Patient-derived tumor xenograft (PDX) (humanized) mouse models represent useful tools for preclinical evaluation of new therapies and biomarker identification...
2020: Frontiers in Immunology
Misun Kim, Hyein Jo, Yoojung Kwon, Youngmi Kim, Hyun Suk Jung, Dooil Jeoung
Homoharringtonine (HHT) is a drug for treatment of chronic myeloid leukemia. However, the role of HHT in allergic inflammations remains unknown. Mouse model of atopic dermatitis (AD) induced by 2, 4,-dinitroflurobenzene (DNFB) and anaphylaxis employing 2,4-dinitropheny-human serum albumin (DNP-HSA) were used to examine the role of HHT in allergic inflammations. HHT inhibited in vitro allergic reactions and attenuated clinical symptoms associated with AD. DNFB induced features of allergic reactions in rat basophilic leukemia (RBL2H3) cells...
2020: Frontiers in Pharmacology
Maolin Ge, Dan Li, Zhi Qiao, Yan Sun, Ting Kang, Shouhai Zhu, Shifen Wang, Hua Xiao, Chunjun Zhao, Shuhong Shen, Zhenshu Xu, Han Liu
MLL undergoes multiple distinct chromosomal translocations to yield aggressive leukemia with dismal outcomes. Besides their well-established role in leukemogenesis, MLL fusions also possess latent tumor-suppressive activity, which can be exploited as effective cancer treatment strategies using pharmacological means such as proteasome inhibitors (PIs). Here, using MLL-rearranged xenografts and MLL leukemic cells as models, we show that wild-type MLL is indispensable for the latent tumor-suppressive activity of MLL fusions...
July 30, 2020: Oncogene
Waitman K Aumann, Jessica L Heath, Amanda E Conway, Sei-Gyung Kim Sze, Veerain K Gupta, Rafi R Kazi, Donald R Tope, Daniel S Wechsler, Catherine P Lavau
No abstract text is available yet for this article.
July 30, 2020: Leukemia
A Sutra Del Galy, A Marouf, E Raffoux, M Robin, D Michonneau, M Sébert, F Sicre de Fontebrune, A Xhaard, E Lengline, R Itzykson, C Frieri, H Dombret, P Fenaux, R Peffault de Latour, L Adès, G Socié
No abstract text is available yet for this article.
July 30, 2020: Leukemia
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