Journal of Hematology & Oncology

http://www.jhoonline.org/

List of Papers (Total 782)

Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL

Background GATA3 is pivotal for the development of T lymphocytes. While its effects in later stages of T cell differentiation are well recognized, the role of GATA3 in the generation of early T cell precursors (ETP) has only recently been explored. As aberrant GATA3 mRNA expression has been linked to cancerogenesis, we investigated the role of GATA3 in early T cell precursor acute ...

Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells

Background The poor outcomes for patients diagnosed with acute myeloid leukemia (AML) are largely attributed to leukemia stem cells (LSCs) which are difficult to eliminate with conventional therapy and responsible for relapse. Thus, new therapeutic strategies which could selectively target LSCs in clinical leukemia treatment and avoid drug resistance are urgently needed. However, ...

Heterogeneity of CD34 and CD38 expression in acute B lymphoblastic leukemia cells is reversible and not hierarchically organized

The existence and identification of leukemia-initiating cells in adult acute B lymphoblastic leukemia (B-ALL) remain controversial. We examined whether adult B-ALL is hierarchically organized into phenotypically distinct subpopulations of leukemogenic and non-leukemogenic cells or whether most B-ALL cells retain leukemogenic capacity, irrespective of their immunophenotype profiles. ...

Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma

Background Patient derived xenografts (PDX) are generated by transplanting the original patient’s tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC) is a deadly form of ovarian/fallopian tube cancer whose ...

NT1014, a novel biguanide, inhibits ovarian cancer growth in vitro and in vivo

Background NT1014 is a novel biguanide and AMPK activator with a high affinity for the organic cation-specific transporters, OCT1 and OCT3. We sought to determine the anti-tumorigenic effects of NT1014 in human ovarian cancer cell lines as well as in a genetically engineered mouse model of high-grade serous ovarian cancer. Methods The effects of NT1014 and metformin on cell ...

Bmi-1 regulates stem cell-like properties of gastric cancer cells via modulating miRNAs

Background B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) plays an important role in regulating stemness in some kinds of cancer. However, the mechanisms remain unclear. This study was to investigate whether and how Bmi-1 regulates stemness of gastric cancer. Methods We firstly explored the role of Bmi-1 in regulating stem cell-like features in gastric ...

Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study

Background Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated. Methods We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients ...

Extensive next-generation sequencing analysis in chronic lymphocytic leukemia at diagnosis: clinical and biological correlations

Background In chronic lymphocytic leukemia (CLL), next-generation sequencing (NGS) analysis represents a sensitive, reproducible, and resource-efficient technique for routine screening of gene mutations. Methods We performed an extensive biologic characterization of newly diagnosed CLL, including NGS analysis of 20 genes frequently mutated in CLL and karyotype analysis to assess ...

Minimal residual disease- and graft-vs.-host disease-guided multiple consolidation chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant

Background Persons with acute leukemia relapsing after allotransplant and who respond to anti-leukemia interventions are at high risk of a second relapse. We studied the impact of minimal residual disease (MRD)- and graft-vs.-host disease (GvHD)-guided multiple consolidation chemotherapy and donor lymphocyte infusions (DLIs) to prevent second relapse in patients with acute leukemia ...

Serial cfDNA assessment of response and resistance to EGFR-TKI for patients with EGFR-L858R mutant lung cancer from a prospective clinical trial

Background Detecting epidermal growth factor receptor (EGFR) activating mutations in plasma could guide EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment for advanced non-small cell lung cancer (NSCLC). However, dynamic quantitative changes of plasma EGFR mutations during the whole course of EGFR-TKI treatment and its correlation with clinical outcomes were not determined. The ...

Aberrant splicing and drug resistance in AML

The advent of next-generation sequencing technologies has unveiled a new window into the heterogeneity of acute myeloid leukemia (AML). In particular, recurrent mutations in spliceosome machinery and genome-wide aberrant splicing events have been recognized as a prominent component of this disease. This review will focus on how these factors influence drug resistance through ...

PEG-aspargase and DEP regimen combination therapy for refractory Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis

Background Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is the most frequent subtype of secondary HLH triggered by infections. Previous studies have shown that ~30 % or more of patients with EBV-HLH do not respond to standard therapy. This study investigated the efficacy and safety profile of a modified DEP regimen in combination with PEG-aspargase ...

Modification of platinum sensitivity by KEAP1/NRF2 signals in non-small cell lung cancer

Background The objective of this study was to evaluate the effect of platinum-based drugs on nuclear-factor erythroid2 like 2 (NRF2) signaling in non-small cell lung cancer cell lines with or without Kelch-like ECH-associated protein 1 (KEAP1) mutations and to determine the role of NRF2 and KEAP1 on platinum-based drug treatment. Methods We used real-time PCR to assess relative ...

Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML) and acute lymphocytic leukaemia (ALL). Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with ...

Selective inhibition of autoimmune exacerbation while preserving the anti-tumor clinical benefit using IL-6 blockade in a patient with advanced melanoma and Crohn’s disease: a case report

Background Novel immunotherapies, or checkpoint inhibitors, targeting programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) have significantly improved outcomes for patients with numerous different cancer types. However, owing to their exclusion from clinical trials and risk for autoimmune exacerbation on these treatments, the impact on ...

Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT

Background Optimal post-remission strategy for patients with acute myeloid leukemia (AML) is matter of intense debate. Recent reports have shown stronger anti-leukemic activity but similar survival for allogeneic stem cell transplantation (allo-HSCT) from matched sibling donor compared to autologous transplantation (auto-HSCT); however, there is scarcity of literature confronting ...

Second-generation inhibitors of Bruton tyrosine kinase

Bruton tyrosine kinase (BTK) is a critical effector molecule for B cell development and plays a major role in lymphoma genesis. Ibrutinib is the first-generation BTK inhibitor. Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib. Resistance to ibrutinib was also reported. The C481S mutation in the BTK kinase domain ...

A three-gene expression-based risk score can refine the European LeukemiaNet AML classification

Background Risk stratification based on cytogenetics of acute myeloid leukemia (AML) remains imprecise. The introduction of novel genetic and epigenetic markers has helped to close this gap and increased the specificity of risk stratification, although most studies have been conducted in specific AML subpopulations. In order to overcome this limitation, we used a genome-wide ...

Immune phenotypes predict survival in patients with glioblastoma multiforme

Background Glioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM. Methods Immune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow ...

A new mechanism of trastuzumab resistance in gastric cancer: MACC1 promotes the Warburg effect via activation of the PI3K/AKT signaling pathway

Background Trastuzumab, a humanized antibody targeting HER2, exhibits remarkable therapeutic efficacy against HER2-positive gastric cancer. However, recurrent therapeutic resistance presents revolutionary claims. Warburg effect and AKT signaling pathway was involved in the resistance to trastuzumab. Our previous studies have demonstrated that overexpression of metastasis associated ...

Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro

Background Multiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO)-receptor (EPOR) signaling is central in various cancers, but the relevance of EPOR signaling in multiple myeloma cells has not yet been thoroughly investigated. Methods Myeloma cell ...

Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains one of the most common and lethal malignancies worldwide despite the development of various therapeutic strategies. A better understanding of the mechanisms responsible for HCC initiation and progression is essential for the development of more effective therapies. The cancer stem cell (CSC) model has provided new insights into the development ...

Treatment of acquired drug resistance in multiple myeloma by combination therapy with XPO1 and topoisomerase II inhibitors

Background Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease. Methods We investigated whether the ...

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the ...

Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery

Background The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT) promotes hematopoiesis by inducing HSC proliferation. Methods We conducted a phase I/II trial of plerixafor on hematopoietic ...