Treatment-free remission (TFR) has become a therapeutic objective for selected chronic-phase chronic myeloid leukemia (CP CML). However, no standardized biomarker is yet in clinical use. In this multi-center study, we explored the potential of bone marrow (BM) cytomorphology given its global accessibility and integral role in clinical diagnostics. We included diagnostic BM...
GATA2 deficiency is a monogenic transcriptopathy disorder characterized by bone marrow failure (BMF), immunodeficiency, and a high risk of developing myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). Although informative mouse models have been developed, the mechanisms by which GATA2 haploinsufficiency drives disease initiation in humans remain incompletely...
Infections are a major cause of morbidity and mortality in multiple myeloma (MM). While increased infection risk has been shown in monoclonal gammopathy of undetermined significance (MGUS), data are limited for smoldering multiple myeloma (SMM). We used data from the iStopMM study, which screened 75,422 Icelandic individuals aged ≥40 years for MM precursors. Individuals diagnosed...
Male sex is associated with worse outcome in acute myeloid leukemia (AML) in many studies. We analyzed the survival of 4281 patients treated with intensive chemotherapy in the AML17 and AML19 trials based on sex. Men had a significantly lower remission rate than women. Men had a higher incidence of adverse cytogenetic features and a lower incidence of the relatively favorable...
Acute lymphoblastic leukemia (ALL) preferentially localizes in the bone marrow (BM) and displays recurrent patterns of medullary and extra-medullary involvement. Leukemic cells exploit their niche for propagation and survive selective pressure by chemotherapy in the BM microenvironment, suggesting the existence of protective mechanisms. Here, we established a three-dimensional...
At present there is no metabolic characterization of acute promyelocytic leukemia (APL). Pathognomonic of APL, PML::RARα fusion protein rewires metabolic pathways to feed anabolic tumor cell’s growth. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapies render APL the most curable subtype of AML, yet approximately 1% of cases are resistant and 5% relapse. We...
Hematopoietic malignancies (HM) represent the most common form of pediatric cancer with lymphoid malignancies being the predominant subtype in kids. The majority of lymphoid malignancies are proposed to occur sporadically with environmental, infectious and inflammatory triggers impacting oncogenesis in ways that are not yet fully understood. With the increased adoption of...
Venetoclax plus azacitidine is recognized as standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC). However, some patients may still not be treated with venetoclax combinations due to frailty concerns. We evaluated efficacy and safety of venetoclax plus azacitidine vs. placebo plus azacitidine in patients with newly diagnosed...
While allogeneic stem cell transplantation (allo-SCT) is the preferred consolidation for high and most intermediate-risk acute myeloid leukemia (AML) patients in first remission, the role of autologous SCT (auto-SCT) vs. chemotherapy (CT) when allo-SCT is not feasible or indicated, remains controversial. We conducted a real-world, retrospective cohort study using the PETHEMA AML...
Multiple myeloma (MM) is a malignancy of immunoglobulin-secreting plasma cells that represents 10% of all hematological cancers and remains essentially incurable, despite recent advances. Long non-coding RNAs (lncRNAs) are an important class of regulatory molecules that have been strongly implicated in the aetiology of MM. Colorectal Neoplasia Differentially Expressed (CRNDE) is...
We performed a questionnaire-based cross-sectional study to analyze Acute Myeloid Leukemia (AML) long-term survivor (LTS) outcomes, including psychosocial well-being and somatic health status. Four-hundred-twenty-seven former AML patients participated (response rate, 63%) ≥5 years[y] and up to 18.6 y past their leukemia diagnosis (median, 11.3 y). Median age at study...
Wilms tumor 1 (WT1) is a tumor-associated antigen expressed in solid tumors and hematological malignancies. T-cell immunotherapies targeting WT1 are currently under development. To analyze endogenous T-cell responses against WT1, we trained computational models capable of detecting WT1-specific T-cell responses from T-cell receptor (TCR) sequencing data. We peptide-pulsed healthy...
Erdheim–Chester Disease (ECD) is a rare histiocytosis characterized by a wide spectrum of clinical manifestations. Although somatic mutations have been involved in ECD, its etiology remains poorly understood. This study aimed to identify novel molecular mechanisms involved in ECD through the first integrated methylome and transcriptome analysis. Peripheral blood samples were...
Current therapeutic options for myelodysplastic neoplasms (MDS)-associated thrombocytopenia are limited. Megakaryocyte maturation might be an innovative therapeutic strategy because its dysregulation profoundly contributes to MDS pathogenesis. Here, we identified crizotinib, a clinically approved anti-cancer drug for anaplastic lymphoma kinase (ALK)-positive non-small-cell lung...
Persistence of JAK2-mutated clones that may undergo clonal evolution and malignant transformation remains a challenge in myeloproliferative neoplasms (MPN), Novel therapeutic approaches to attenuate clonal evolution and progression to blast-phase are therefore urgently needed. LSD1 (KDM1A) inhibitors reduce symptoms and clonal burden in MPN, but whether these compounds may be...
Donor age is one factor to optimize allogeneic hematopoietic cell transplantation (alloHCT). Therefore, we investigated whether young unrelated donors (UD) provide a benefit for older patients with myeloid malignancies compared to HLA-identical sibling donors (MSD). We performed a retrospective registry study on patients ≥50 years who received a first alloHCT between 2010 and...
Despite the remarkable clinical successes of chimeric antigen receptor (CAR) T-cell therapies in treating B-cell malignancies and multiple myeloma, similar outcomes have not been achieved in other indications. For patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or T-cell acute lymphoblastic leukemia (T-ALL), treatment options are limited, yet CART-cell...