Journal of Hematology & Oncology

http://www.jhoonline.org/

List of Papers (Total 751)

Short telomere length and its correlation with gene mutations in myelodysplastic syndrome

Background Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been ...

Immunoprofiling of leukemic stem cells CD34+/CD38−/CD123+ delineate FLT3/ITD-positive clones

Background Acute myeloid leukemia (AML) is a heterogeneous clonal disorder presenting with accumulation of proliferating undifferentiated blasts. Xenograft transplantation studies have demonstrated a rare population of leukemia-initiating cells called leukemic stem cells (LSCs) capable of propagating leukemia that are enriched in the CD34+/CD38− fraction. LSCs are quiescent, ...

Risk of venous thromboembolism in hospitalised cancer patients in England—a cohort study

Background Venous thromboembolism (VTE) is a well-recognised and life-threatening complication in patients with cancer. However, the precise risk of VTE in hospitalised cancer patients in England has not been previously reported. Methods We conducted a cohort study using linked Hospital Episodes Statistics and Office for National Statistics mortality data. We determined the risk of ...

Chasing the precursor of functional hematopoietic stem cells at the single cell levels in mouse embryos

Background Adult hematopoietic stem cells (HSCs), the ideal system for regenerative research, were isolated at single cell levels decades ago, whereas studies on embryonic HSCs are much more difficult. Methods Zhou et al identified a new pre-HSC cell surface marker, CD201, by which they isolated pre-HSCs at single cell levels for further analyses. Results The novel expression ...

EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer

T790M mutation is the most common mechanism for resistance to first- and second-generation tyrosine kinase inhibitors (TKI) for epidermal growth factor receptor (EGFR). Several third-generation EGFR mutant selective TKIs are being explored to conquer this resistance. AZD9291 (osimertinib, tagrisso) has been approved for treatment of the metastatic EGFR T790M mutation-positive ...

Decreased expression of the long noncoding RNA LINC00261 indicate poor prognosis in gastric cancer and suppress gastric cancer metastasis by affecting the epithelial–mesenchymal transition

Background Recent evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles in the regulation of cellular processes and are found to be dysregulated in a variety of cancers. LINC00261 is an lncRNA that is aberrantly expressed in gastric cancer (GC). The clinical role of LINC00261 in GC and molecular mechanisms remains to be found. Methods Real-time polymerase chain ...

Effective adoptive immunotherapy of triple-negative breast cancer by folate receptor-alpha redirected CAR T cells is influenced by surface antigen expression level

Background The poor prognosis and the limited efficacy of targeted therapy in patients with triple-negative breast cancer (TNBC) have raised the need for alternative therapies. Recent studies have demonstrated that folate receptor-alpha (FRα) may represent an ideal tumor-associated marker for immunotherapy for TNBC. Methods The aim of the present study was to apply a chimeric ...

Elotuzumab for the treatment of multiple myeloma

Elotuzumab is one of the first two monoclonal antibodies that gained FDA approval for the treatment of multiple myeloma (MM). It targets SLAMF7, which is highly expressed in normal plasma and MM cells as well as natural killer (NK) cells. Elotuzumab demonstrated significant anti-myeloma activity in preclinical studies, and its mechanisms of action include mediating ...

Pooled analysis of the reports of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma

Purpose The purpose of this study was to better understand the efficacy and safety of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma(R/RMM). Methods We retrieved and reviewed published reports including carfilzomib, panobinostat, and elotuzumab combination regimens for patients with R/RMM. Results We identified 20 ...

Azacytidine mitigates experimental sclerodermic chronic graft-versus-host disease

Background Previous studies have demonstrated that regulatory T cells (Tregs) play a protective role in the pathogenesis of chronic graft-versus-host disease (cGVHD). Tregs constitutively express the gene of the transcription factor Foxp3 whose CNS2 region is heavily methylated in conventional CD4 + T cells (CD4 + Tconvs) but demethylated in Tregs. Methods Here, we assessed the ...

Daratumumab: a first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma

Daratumumab is a human monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on multiple myeloma (MM) cells. Preclinical studies have shown that daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis ...

Novel agents in the treatment of multiple myeloma: a review about the future

Multiple myeloma (MM) is a disease that affects plasma cells and can lead to devastating clinical features such as anemia, lytic bone lesions, hypercalcemia, and renal disease. An enhanced understanding of MM disease mechanisms has led to new more targeted treatments. There is now a plethora of treatments available for MM. In this review article, our aim is to discuss many of the ...

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

Background Venetoclax, a small molecule BH3 mimetic which inhibits the anti-apoptotic protein Bcl-2, and idasanutlin, a selective MDM2 antagonist, have both shown activity as single-agent treatments in pre-clinical and clinical studies in acute myeloid leukemia (AML). In this study, we deliver the rationale and molecular basis for the combination of idasanutlin and venetoclax for ...

Targeting histone methylation for cancer therapy: enzymes, inhibitors, biological activity and perspectives

Post-translational methylation of histone lysine or arginine residues plays important roles in gene regulation and other physiological processes. Aberrant histone methylation caused by a gene mutation, translocation, or overexpression can often lead to initiation of a disease such as cancer. Small molecule inhibitors of such histone modifying enzymes that correct the abnormal ...

Programmed cell death-1 blockade in recurrent disseminated Ewing sarcoma

Background Ewing sarcoma (EWS) is a malignant tumour of bone and soft tissue, and although many patients are cured with conventional multimodal therapy, those with recurrent or metastatic disease have a poor prognosis. Genomic instability and programmed cell death ligand-1 (PD-L1) expression have been identified in EWS, providing a rationale for treatment with agents that block the ...

Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy

Modulating immune inhibitory pathways has been a major recent breakthrough in cancer treatment. Checkpoint blockade antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programed cell-death protein 1 (PD-1) have demonstrated acceptable toxicity, promising clinical responses, durable disease control, and improved survival in some patients with advanced melanoma, ...

The clinical application of mesenchymal stromal cells in hematopoietic stem cell transplantation

Mesenchymal stromal cells (MSCs) are multipotent stem cells well known for repairing tissue, supporting hematopoiesis, and modulating immune and inflammation response. These outstanding properties make MSCs as an attractive candidate for cellular therapy in immune-based disorders, especially hematopoietic stem cell transplantation (HSCT). In this review, we outline the progress of ...

Calreticulin-mutant proteins induce megakaryocytic signaling to transform hematopoietic cells and undergo accelerated degradation and Golgi-mediated secretion

Background Somatic calreticulin (CALR), Janus kinase 2 (JAK2), and thrombopoietin receptor (MPL) mutations essentially show mutual exclusion in myeloproliferative neoplasms (MPN), suggesting that they activate common oncogenic pathways. Recent data have shown that MPL function is essential for CALR mutant-driven MPN. However, the exact role and the mechanisms of action of CALR ...

PU.1 controls the expression of long noncoding RNA HOTAIRM1 during granulocytic differentiation

Background Long noncoding RNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) has been characterized as a critical factor in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells. However, the essential transcription factor for gene expression of HOTAIRM1 is still unknown. Findings Chromatin immunoprecipitation (ChIP) assays revealed ...

iPSC-derived mesenchymal stromal cells are less supportive than primary MSCs for co-culture of hematopoietic progenitor cells

In vitro culture of hematopoietic stem and progenitor cells (HPCs) is supported by a suitable cellular microenvironment, such as mesenchymal stromal cells (MSCs)—but MSCs are heterogeneous and poorly defined. In this study, we analyzed whether MSCs derived from induced pluripotent stem cells (iPS-MSCs) provide a suitable cellular feeder layer too. iPS-MSCs clearly supported ...

Lung tumor exosomes induce a pro-inflammatory phenotype in mesenchymal stem cells via NFκB-TLR signaling pathway

Background In tumor microenvironment, a continuous cross-talk between cancer cells and other cellular components is required to sustain tumor progression. Accumulating evidence suggests that exosomes, a novel way of cell communication, play an important role in such cross-talk. Exosomes could facilitate the direct intercellular transfer of proteins, lipids, and miRNA/mRNA/DNAs ...

Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia

Background Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance. Methods To further investigate the association between CDKN2 status and TKI resistance, the prevalence of CDKN2 deletions and its correlation ...

l-asparaginase-based regimens followed by allogeneic hematopoietic stem cell transplantation improve outcomes in aggressive natural killer cell leukemia

Aggressive nature killer cell leukemia (ANKL) is a mature NK-T cell lymphoma with worse prognosis, but optimal treatment is unclear. Therefore, we analyzed the efficacy of l-asparaginase-based regimens for ANKL patients. Twenty-one patients who received dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) or etoposide, ifosfamide, dexamethasone, and ...

Azacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications

Background The MDS-IWG and NCCN currently endorse both FAB and WHO classifications of MDS and AML, thus allowing patients with 20–30 % bone marrow blasts (AML20–30, formerly MDS-RAEB-t) to be categorised and treated as either MDS or AML. In addition, an artificial distinction between AML20–30 and AML30+ was made by regulatory agencies by initially restricting approval of ...

How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation?

In haploidentical stem cell transplantations (haplo-SCT), nearly all patients have more than one donor. A key issue in the haplo-SCT setting is the search for the best donor, because donor selection can significantly impact the incidences of acute and chronic graft-versus-host disease, transplant-related mortality, and relapse, in addition to overall survival. In this review, we ...