-
Article
Open AccessThe landscape of RNA-chromatin interaction reveals small non-coding RNAs as essential mediators of leukemia maintenance
RNA constitutes a large fraction of chromatin. Spatial distribution and functional relevance of most of RNA-chromatin interactions remain unknown. We established a landscape analysis of RNA-chromatin interacti...
-
Article
Open AccessThe landscape of small nucleolar RNA expression in multiple myeloma is determined by cytogenetic alterations
-
Article
Open AccessThe ribosomal protein S6 kinase alpha-1 (RPS6KA1) induces resistance to venetoclax/azacitidine in acute myeloid leukemia
Venetoclax/azacitidine combination therapy is effective in acute myeloid leukemia (AML) and tolerable for older, multimorbid patients. Despite promising response rates, many patients do not achieve sustained r...
-
Article
Open AccessProtein tyrosine kinase 2b inhibition reverts niche-associated resistance to tyrosine kinase inhibitors in AML
FLT3 tyrosine kinase inhibitor (TKI) therapy evolved into a standard therapy in FLT3-mutated AML. TKI resistance, however, develops frequently with poor outcomes. We analyzed acquired TKI resistance in AML cel...
-
Article
AKTing on XPO1 inhibition in AML
Inhibition of XPO1-mediated nuclear export by selinexor represents a promising therapeutic strategy in acute myeloid leukemia. Because XPO1 is not specific for tumor-suppressive proteins, selinexor may also ac...
-
Article
Open AccessIntegrated RNAi screening identifies the NEDDylation pathway as a synergistic partner of azacytidine in acute myeloid leukemia
Treatment of acute myeloid leukemia (AML) remains challenging and novel targets and synergistic therapies still need to be discovered. We performed a high-throughput RNAi screen in three different AML cell lin...
-
Article
Hotspot DNMT3A mutations in clonal hematopoiesis and acute myeloid leukemia sensitize cells to azacytidine via viral mimicry response
Somatic mutations in DNA methyltransferase 3A (DNMT3A) are among the most frequent alterations in clonal hematopoiesis (CH) and acute myeloid leukemia (AML), with a hotspot in exon 23 at arginine 882 (DNMT3AR882)...
-
Article
A proof of concept phase I/II pilot trial of LSD1 inhibition by tranylcypromine combined with ATRA in refractory/relapsed AML patients not eligible for intensive therapy
All-trans-retinoic acid (ATRA) is highly active in acute promyelocytic leukemia but not in other types of acute myeloid leukemia (AML). Previously, we showed that ATRA in combination with Lysine-specific demet...
-
Article
Open AccessNOP10 predicts lung cancer prognosis and its associated small nucleolar RNAs drive proliferation and migration
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide underlining the urgent need for new biomarkers and therapeutic targets for this disease. Long noncoding RNAs are critical playe...
-
Article
Open AccessIntegrated analysis of relapsed B-cell precursor Acute Lymphoblastic Leukemia identifies subtype-specific cytokine and metabolic signatures
Recent efforts reclassified B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) into more refined subtypes. Nevertheless, outcomes of relapsed BCP-ALL remain unsatisfactory, particularly in adult patients ...
-
Article
Open AccessLong non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia
Long non-coding RNAs (lncRNAs) have emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. However, the role and expression pattern of lncRNAs in molecular subtypes...
-
Article
AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia
Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2′-O-methylation as ...
-
Article
Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia
Proteasomal degradation of EZH2 in AML patients in response to therapy triggers the expression of stem cell markers and has been identified as an epigenetic pathway leading to acquired drug resistance. Treatme...
-
Article
Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia
Drugs that induce redifferentiation of cancer cells are efficient only in some subtypes of AML. The authors show that sensitivity to pro-differentiation drugs such as ATRA can be induced by co-treatment with e...
