The Latest Haemato-Oncology Journal Articles
Keep up to date with the latest in haemato-oncology. Check out the latest haemato-oncology articles from leading medical journals in a single view, helping you discover relevant articles quickly and easily
- Loss of interleukin-10 activates innate immunity to eradicate adult T cell leukemia initiating cells.Adult T cell leukemia/lymphoma (ATL) is associated to chronic human T cell leukemia virus type 1 (HTLV-1) infection and carries a poor prognosis. Arsenic trioxide (AS) and interferon-alpha (IFNα) together selectively trigger Tax viral oncoprotein degradation and cure Tax-driven murine ATL. AS/IFNα/zidovudine treatment achieves a high response rate in patients with chronic ATL. Interleukin 10 […]
- Methotrexate-related central neurotoxicity: clinical characteristics, risk factors and genome-wide association study in children treated for acute lymphoblastic leukemia.Symptomatic methotrexate-related central neurotoxicity, ‘MTX neurotoxicity’, is a severe toxicity experienced during acute lymphoblastic leukemia (ALL) therapy with potential long-term neurologic complications. Risk factors and long-term outcomes require further study. We conducted a systematic, retrospective review of 1251 consecutive Australian children enrolled on BFM or COG-based protocols between 1998-2013. Clinical risk predictors for MTX neurotoxicity […]
- A phase I/II study of the combination of panobinostat and carfilzomib in patients with relapsed or relapsed/refractory multiple myeloma: Final analysis of second dose-expansion cohort.The maximum tolerated dose of the panobinostat and carfilzomib combination in patients with relapsed/refractory multiple myeloma (RRMM) was not reached in our previous dose-escalation study. We report additional dose levels in the phase I/II, single-arm, multicenter, standard 3+3 dose-escalation expansion-cohort study (NCT01496118). Patients with RRMM were treated with panobinostat 30 mg, carfilzomib 20/56 mg/m2 (N = 3), […]
- Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome After CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial.To prospectively evaluate the effectiveness of risk-adapted preemptive tocilizumab (PT) administration in preventing severe cytokine release syndrome (CRS) after CTL019, a CD19 chimeric antigen receptor T-cell therapy.Children and young adults with CD19-positive relapsed or refractory B-cell acute lymphoblastic leukemia were assigned to high- (≥ 40%) or low- (< 40%) tumor burden cohorts (HTBC or LTBC) […]
- APR-246 induces early cell death by ferroptosis in acute myeloid leukemia.APR-246 is a promising new therapeutic agent that targets p53 mutated proteins in myelodysplastic syndromes and in acute myeloid leukemia. APR-246 reactivates the transcriptional activity of p53 mutants by facilitating their binding to DNA target sites. Recent studies in solid cancers have found that APR-246 can also induce p53-independent cell death. In this study, we […]
- Consolidation Therapy for Acute Myeloid Leukemia: Defining a Benchmark.The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers […]
- Cost-Effectiveness of First-Line Versus Second-Line Use of Daratumumab in Older, Transplant-Ineligible Patients With Multiple Myeloma.The MAIA trial found that addition of daratumumab to lenalidomide and dexamethasone (DRd) significantly prolonged progression-free survival in transplant-ineligible patients with newly diagnosed multiple myeloma, compared with lenalidomide and dexamethasone alone (Rd). However, daratumumab is a costly treatment and is administered indefinitely until disease progression. Therefore, it is unclear whether it is cost-effective to use […]
- Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children’s Oncology Group AALL0932.AALL0932 evaluated two randomized maintenance interventions to optimize disease-free survival (DFS) while reducing the burden of therapy in children with newly diagnosed NCI standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL).AALL0932 enrolled 9,229 patients with B-ALL; 2,364 average-risk (AR) patients were randomly assigned (2 × 2 factorial design) at the start of maintenance therapy to vincristine/dexamethasone pulses […]
- Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol.Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide).MRD was measured in 249 […]
- New regimens and directions in the management of newly diagnosed multiple myeloma.The introduction of novel agents over the last decade has rapidly expanded the therapeutic landscape of multiple myeloma (MM) for both transplant-eligible and transplant-ineligible patients. The assessment of minimal residual disease (MRD) by next-generation flow cytometry or next-generation sequencing is established as a powerful predictor of long-term outcomes. The use of MRD in response-adapted clinical […]
- Impact of laboratory work-up of lymphoma guidelines on cytopathology practices.A multi-society expert panel recently published evidence-based guidelines and recommendations for the primary diagnosis and classification of lymphoma, which included a public comment period. The guideline concludes: “primary diagnosis and classification of lymphoma can be achieved with a variety of specimens.” The guideline recommends that fine-needle aspiration biopsy (FNAB) cytomorphology not be used without ancillary […]
- Immunophenotypic changes of leukemic blasts in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia, who have been treated with Blinatumomab.Not available. View the full article @ Haematologica Get PDF with LibKey
- Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.Mutations in the gene CBL were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in […]
- CD38 knockout natural killer cells expressing an affinity optimized CD38 chimeric antigen receptor successfully target acute myeloid leukemia with reduced effector cell fratricide.There is a strong biological rationale for the augmentation of allogeneic natural killer (NK) cell therapies with a chimeric antigen receptor (CAR) to enhance acute myeloid leukemia (AML) targeting. CD38 is an established immunotherapeutic target in multiple myeloma and under investigation as a target antigen in AML. CD38 expression on NK cells and its further […]
- Epigenetic changes in human model KMT2A leukemias highlight early events during leukemogenesis.Chromosomal translocations involving KMT2A gene are one of the most common genetic alterations found in pediatric acute myeloid leukemias (AML) although the molecular mechanisms that initiate the disease remain incompletely defined. To elucidate these initiating events we have used a human model system of AML driven by the KMT2A-MLLT3 (KM3) fusion. More specifically, we investigated […]
- Whole genome CRISPR screening identifies TOP2B as a potential target for IMiD sensitization in multiple myeloma.Not available. View the full article @ Haematologica Get PDF with LibKey
- Genome-wide CRISPR screen identifies regulators of MAPK and MTOR pathways mediating sorafenib resistance in acute myeloid leukemia.Drug resistance impedes the long-term effect of targeted therapies in acute myeloid leukemia (AML), necessitating the identification of mechanisms underlying resistance. Approximately 25% of AML patients carry FLT3 mutations and develop post-treatment insensitivity to FLT3 inhibitors, including sorafenib. Using a genome-wide CRISPR screen, we identified LZTR1, NF1, TSC1 or TSC2, negative regulators of the MAPK […]
- Augmented Reduced-Intensity Regimen Does Not Improve Postallogeneic Transplant Outcomes in Acute Myeloid Leukemia.Reduced-intensity conditioning (RIC) regimens have extended the curative potential of allogeneic stem-cell transplantation to older adults with high-risk acute myeloid leukemia (AML) and myelodysplasia (MDS) but are associated with a high risk of disease relapse. Strategies to reduce recurrence are urgently required. Registry data have demonstrated improved outcomes using a sequential transplant regimen, fludarabine/amsacrine/cytarabine-busulphan (FLAMSA-Bu), […]
- Defining the Optimal Total Number of Chemotherapy Courses in Younger Patients With Acute Myeloid Leukemia: A Comparison of Three Versus Four Courses.The optimum number of treatment courses for younger patients with acute myeloid leukemia (AML) is uncertain. The United Kingdom National Cancer Research Institute AML17 trial randomly assigned patients who were not high risk to a total of three versus four courses.Patients received two induction courses based on daunorubicin and cytarabine (Ara-C), usually with gemtuzumab ozogamicin. […]
- Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor.We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML […]
- Determination of Fitness and Therapeutic Options in Older Patients With Acute Myeloid Leukemia.Treatment of older patients with AML remains challenging. Although age, performance status, and comorbidities are commonly employed to determine fitness for intensive treatment, several studies have demonstrated improved outcomes with treatment in older and classically unfit patients, highlighting the importance of other disease- and patient-related factors that have prognostic value for treatment outcome in AML. […]
- Targeting BCL-2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma.Venetoclax (Ven) is a selective small-molecule inhibitor of BCL-2 that exhibits antitumoral activity against MM cells with t(11;14) translocation. We evaluated the safety and efficacy of Ven and dexamethasone (VenDex) combination in patients with t(11;14) positive relapsed/refractory (R/R) multiple myeloma (MM). This open-label, multicenter study had two distinct phases (phase 1 [P1], phase 2 [P2]). […]
- Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission.Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor.We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML […]
- Symptom burden in transplant ineligible patients with newly diagnosed multiple myeloma: a population-based cohort study.Not available. View the full article @ Haematologica Get PDF with LibKey
- Targeting MCL-1 dysregulates cell metabolism and leukemia-stroma interactions and resensitizes acute myeloid leukemia to BCL-2 inhibition.MCL-1 and BCL-2 are both frequently overexpressed in acute myeloid leukemia and critical for the survival of acute myeloid leukemia cells and acute myeloid leukemia stem cells. MCL-1 is a key factor in venetoclax resistance. Using genetic and pharmacological approaches, we discovered that MCL-1 regulates leukemia cell bioenergetics and carbohydrate metabolisms, including the TCA cycle, […]
- Mixed-lineage leukemia protein modulates the loading of let-7a onto AGO1 by recruiting RAN.Not available. View the full article @ Haematologica Get PDF with LibKey
- The impact of early discontinuation/dose modification of venetoclax on outcomes in patients with relapsed/refractory chronic lymphocytic leukemia: post-hoc analyses from the phase III MURANO study.Fixed-duration venetoclax plus rituximab (VenR) has a manageable safety profile and improves survival in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). We present data from the phase III MURANO study on the impact of venetoclax modification or premature discontinuation on outcomes in patients with R/R CLL. Time-dependent Cox proportional hazards regression models, stratified by […]
- Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study.Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients.FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients ≤ 18 years at […]
- Immune Checkpoint Programmed Cell Death Protein-1 (PD-1) Expression on Bone Marrow T Cell Subsets in Patients With Plasma Cell Myeloma.Plasma cell myeloma (PCM) is caused by immune dysregulation. We evaluated the expression of immune checkpoint programmed cell death protein-1 (PD-1) on T cell subsets in PCM patients according to disease course and cytogenetic abnormalities. This study aimed to find a target group suitable for therapeutic use of PD-1 blockade in PCM.A total of 188 […]
- CDKN2A deletions are associated with poor outcomes in 101 adults with T-cell acute lymphoblastic leukemia.The identification of genetic risk subgroups of T-cell acute lymphoblastic leukemia (T-ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T-ALL. CDKN2A deletion was present in 23% (23/101) of T-ALL by fluorescence in situ hybridization (FISH). The […]
- Efficacy and safety of oral panobinostat plus subcutaneous bortezomib and oral dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma (PANORAMA 3): an open-label, randomised, phase 2 study.Improved therapeutic options are needed for patients with relapsed or relapsed and refractory multiple myeloma. Subcutaneous bortezomib has replaced intravenous bortezomib as it is associated with a more favourable toxicity profile. We investigated the activity and safety of three different dosing regimens of oral panobinostat in combination with subcutaneous bortezomib and oral dexamethasone for this […]
- Shallow-depth sequencing of cell-free DNA for Hodgkin and diffuse large B-cell lymphoma (differential) diagnosis: a standardized approach with underappreciated potential.Shallow-depth sequencing of cell-free DNA, a cheap and standardized approach to obtain molecular information on tumors non-invasively, is insufficiently explored for lymphoma diagnosis and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non- HL patients, […]
- Minimal residual disease monitoring in acute myeloid leukemia with non-A/B/D-NPM1 mutations by digital polymerase chain reaction: feasibility and clinical use.Not available. View the full article @ Haematologica Get PDF with LibKey
- Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated E. coli asparaginase in children with acute lymphocytic leukemia.Antibodies against polyethylene glycol (PEG) in healthy subjects raise concerns about the efficacy of pegylated drugs. We evaluated the prevalence of antibodies against PEG among patients with acute lymphoblastic leukemia (ALL) prior to and/or immediately after their first dose of pegylated E.coli asparaginase (PEG-ASNase). Serum samples of 701 children, 673 with primary ALL, 28 with […]
- Phenogenomic heterogeneity of post-transplant plasmablastic lymphomas.Plasmablastic lymphoma (PBL) is a rare and clinically aggressive neoplasm that typically occurs in immunocompromised individuals, including those with HIV infection and solid organ allograft recipients. Most prior studies have focused on delineating the clinicopathologic features and genetic attributes of HIV-related PBLs, where MYC deregulation and EBV infection, and more recently, mutations in JAK/STAT, MAP […]
- Autologous stem cell transplantation is safe and effective for fit older myeloma patients: exploratory results from the Myeloma XI trial.Autologous stem cell transplant (ASCT) remains standard of care for consolidation after induction therapy for eligible newly diagnosed myeloma patients. In recent clinical trials comparing ASCT to delayed ASCT, patients aged over 65 were excluded. In real-world practice stem cell transplants are not restricted to those aged under 65 and clinicians decide on transplant eligibility […]
- Impact of luteinizing hormone suppression on hematopoietic recovery after intensive chemotherapy in patients with leukemia.Treatment of acute leukemia with intensive chemotherapy leads to an increased risk of myelosuppression. Luteinizing hormone (LH) blockade improves hematopoietic recovery in mice after radiation or chemotherapy, through protection of the hematopoietic stem cells which express the LH receptor. We hypothesized that LH blockade improves hematopoietic recovery following intensive chemotherapy in patients with leukemia. We […]
- Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma.Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need.Patients with RRMM refractory to pomalidomide and/or an […]
- Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase ii pediatric-like gimema lal-1308 trial.Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric-inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP-BFM ALL 2000-based regimen – the GIMEMA LAL-1308 protocol – for newly diagnosed AYA (range 18-35 years) […]
- CRISPR screen identifies genes that sensitize AML cells to double negative T cell therapy.Acute myeloid leukemia (AML) remains a devastating disease in need of new therapies to improve patient survival. Targeted, adoptive T cell therapies have achieved impressive clinical outcomes in some B-cell leukemias and lymphomas but not in AML. Double negative T cells (DNTs) effectively kill blast cells from the majority of AML patients and are now […]
- Clinical effects of administering leukemia-specific donor T cells to patients with AML/MDS post-allogeneic transplant.Relapse after allogeneic hematopoietic stem-cell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Infusions of unselected donor lymphocytes (DLIs) are used to enhance the graft-versus-leukemia (GVL) effect, as treatment for relapsed disease. However, as the infused lymphocytes are not selected for leukemia-specificity, the GVL […]
- Venetoclax with Decitabine Versus Intensive Chemotherapy in Acute Myeloid Leukemia: A Propensity Score Matched Analysis Stratified by Risk of Treatment-related Mortality.Hypomethylating agents (HMA) with venetoclax is a new standard for older/unfit patients with acute myeloid leukemia (AML). However, it is unknown how HMA with venetoclax compare to intensive chemotherapy (IC) in patients who are ‘fit’ or ‘unfit’ for IC. We compared outcomes of older patients with newly diagnosed AML receiving 10-day decitabine with venetoclax (DEC10-VEN) […]
- IDH1 mutation contributes to myeloid dysplasia in mice by disturbing heme biosynthesis and erythropoiesis.Isocitrate dehydrogenase (IDH) mutations are common genetic alterations in myeloid disorders, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Epigenetic changes, including abnormal histone and DNA methylation, have been implicated in the pathogenic build-up of hematopoietic progenitors, but it is still unclear whether and how IDH mutations themselves affect hematopoiesis. Here, we show that […]
- How to manage CML patients with comorbidities.Patients with chronic myeloid leukemia (CML) often have comorbidities, at an incidence that might be higher than in the general population. Because of the favorable outcome of most patients with CML treated with tyrosine kinase inhibitors (TKIs), a greater number of comorbidities might be the most significant adverse feature for long-term survival. The presence of […]
- Endogenous and combination retinoids are active in myelomonocytic leukemias.Retinoid therapy transformed response and survival outcomes in acute promyelocytic leukemia (APL), but has demonstrated only modest activity in non-APL forms of acute myeloid leukemia (AML). The presence of natural retinoids in vivo could influence the efficacy of pharmacologic agonists and antagonists. We found that natural RXRA ligands, but not RARA ligands, were present in […]
- The epigenetic regulator RINF (CXXC5) maintains SMAD7 expression in human immature erythroid cells and sustains red blood cells expansion.The gene CXXC5, encoding a Retinoid-Inducible Nuclear Factor (RINF), is located within a region at 5q31.2 commonly deleted in myelodysplastic syndrome (MDS) and adult acute myeloid leukemia (AML). RINF may act as an epigenetic regulator and has been proposed as a tumor suppressor in hematopoietic malignancies. However, functional studies in normal hematopoiesis are lacking, and […]
- Persistent Challenges with Treating Multiple Myeloma Early.Over the last decade, two strategies have advanced the treatment of patients with multiple myeloma and precursor diseases. First, the definition has changed to include patients without end organ damage, who previously would not be treated. Second, there is widespread enthusiasm to treat high risk smoldering myeloma. In this commentary, we explore the evidence supporting […]
- Adaptive T-cell immunity controls senescence-prone MyD88- or CARD11-mutant B-cell lymphomas.Aberrant B-cell receptor (BCR)/NF-kB signaling is a hallmark feature of B-cell non-Hodgkin lymphomas (B-NHL), especially in diffuse large B-cell lymphoma (DLBCL). Recurrent mutations in this cascade, e.g. in CD79B, CARD11, or NFKBIZ, and also in the Toll-like receptor pathway transducer MyD88, all deregulate NF-kB, but their differential impact on lymphoma development and biology remains to […]
- Adaptive T-cell immunity controls senescence-prone MyD88- or CARD11-mutant B-cell lymphomas.Aberrant B-cell receptor (BCR)/NF-kB signaling is a hallmark feature of B-cell non-Hodgkin lymphomas (B-NHL), especially in diffuse large B-cell lymphoma (DLBCL). Recurrent mutations in this cascade, e.g. in CD79B, CARD11, or NFKBIZ, and also in the Toll-like receptor pathway transducer MyD88, all deregulate NF-kB, but their differential impact on lymphoma development and biology remains to […]
- Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic and immune evasion programs in ETP-ALL.Lineage plasticity and stemness have been invoked as the cause of therapy resistance in cancer, as these flexible states allow cancer cells to de-differentiate and alter their dependencies. We investigated such resistance mechanisms in relapsed / refractory early T-cell progenitor acute lymphoblastic leukemia carrying activating NOTCH1 mutations, by full-length single cell RNA sequencing of malignant […]
- Final Results of a Phase 1 Study of Loncastuximab Tesirine in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma.The prognosis for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) remains poor, with a need for alternatives to current salvage therapies. Loncastuximab tesirine (ADCT-402) is an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. Presented here are final results of a Phase 1 dose-escalation and dose-expansion […]
- IGLV3-21R110 identifies an aggressive biological subtype of chronic lymphocytic leukemia with intermediate epigenetics.B-cell receptor (BCR) signaling is crucial for chronic lymphocytic leukemia (CLL) biology. IGLV3-21-expressing B-cells may acquire a single point mutation (R110) that triggers autonomous BCR signaling conferring aggressive behavior. Epigenetic studies have defined three CLL subtypes based on methylation signatures reminiscent of naïve-like (n-CLL), intermediate (i-CLL) and memory-like B-cells (m-CLL) with different biological features. i-CLL […]
- A validated pediatric disease risk index for allogeneic hematopoietic cell transplantation.A disease risk index (DRI) that was developed for adults with hematologic malignancy undergoing hematopoietic cell transplant is also being used to stratify children and adolescents by disease risk. Therefore, in this study, we analyzed 2569 patients aged <18 years with acute myeloid (AML; n=1224) or lymphoblastic (ALL; n=1345) leukemia undergoing hematopoietic cell transplant to […]
- Genomic and transcriptomic correlates of Richter’s transformation in Chronic Lymphocytic Leukemia.The transformation of chronic lymphocytic leukemia (CLL) to high-grade B-cell lymphoma is known as Richter’s Syndrome (RS) and it is a rare event with dismal prognosis. In this study, we conducted whole genome sequencing (WGS) of paired circulating CLL (PB-CLL) and RS biopsies (tissue-RS) from 17 clinical trial (CHOP-O) patients. We found that tissue-RS was […]
- CC-90009, a novel cereblon E3 ligase modulator targets acute myeloid leukemia blasts and leukemia stem cells.A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue degraders to eliminate disease-driving proteins. Here, we present the identification of a first-in-class GSPT1-selective cereblon E3 ligase modulator, CC-90009. Biochemical, structural and molecular characterization demonstrates that CC-90009 co-opts the CRL4CRBN to selectively target GSPT1 […]
- Enhanced IL-9 secretion by p66Shc-deficient CLL cells modulates the chemokine landscape of the stromal microenvironment.The stromal microenvironment is central to chronic lymphocytic leukemia (CLL) pathogenesis. How leukemic cells condition the stroma to enhance its chemoattractant properties remains elusive. Here we show that mouse and human CLL cells promote the contact-independent stromal expression of homing chemokines. This function was strongly enhanced in leukemic cells from Em-TCL1 mice lacking the pro-oxidant […]
- Networking for advanced molecular diagnosis in acute myeloid leukemia patients is possible: the PETHEMA NGS-AML project.Next-Generation Sequencing has recently been introduced to efficiently and simultaneously detect genetic variations in acute myeloid leukemia. However, its implementation in the clinical routine raises new challenges focused on the diversity of assays and variant reporting criteria. To overcome this challenge, the PETHEMA group established a nationwide network of reference laboratories aimed to deliver molecular […]
- The LEukemia Artificial Intelligence Program (LEAP) in Chronic Myeloid Leukemia in Chronic Phase: A Model to Improve Patient Outcomes.Extreme gradient boosting methods outperform conventional machine-learning models. Here, we have developed the LEukemia Artificial intelligence Program (LEAP) with the extreme gradient boosting decision tree method for the optimal treatment recommendation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in chronic phase (CML-CP).A cohort of CML-CP patients was randomly divided into training/validation […]
- UTX maintains functional integrity of murine hematopoietic system by globally regulating aging-associated genes.Epigenetic regulation is essential for the maintenance of the hematopoietic system, and its deregulation is implicated in hematopoietic disorders. Here, we show that UTX, a demethylase for lysine 27 on histone H3 (H3K27) and a component of Compass-like and SWI/SNF complexes, plays an essential role in the hematopoietic system by globally regulating aging-associated genes. Utx-deficient […]
- The treatment of Burkitt lymphoma in adults.Burkitt lymphoma (BL) is a highly aggressive, B-cell, non-Hodgkin lymphoma (NHL) categorized into endemic, sporadic and immunodeficiency-associated subtypes. BL has distinct pathologic and clinical features, characterized by rapidly progressive tumors with high rates of extranodal involvement. Next generation sequencing (NGS) analyses have further characterized the genomic landscape of BL and our understanding of disease pathogenesis, […]