I will turn 67, may 1st!.I will not stop doing science and I will keep serving you with our Erasmus Virtual Lectures! .Therefore I will climb the Alp d'Huez to raise money for the Dutch Cancer Foundation. Please support me!.

Read our Spotlight article: One for All and All for One: New Insights into Enhancers Driving MYC Dysregulation .Its a commentary on the very nice paper by Iyer and colleagues!.

RT @dstarczynowski: Thrilled to share our latest research out today in @Nature: “Microbial metabolite drives ageing-related clonal hematopo….

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07 April at 16.00 CET our Erasmus Hematology lecture series that survived COVID continues with:.Daphna Nachmani, from the Hebrew University, Jerusalem, Israel.Titel: "Ribosomal RNA modifications as determinant of HSC function". Link: ID: 827 4734 8072.

Today March 3, at 16.00 CET: Join the Virtual Erasmus Hematology Lecture!.We have Naama Kanarek, from Boston Children’s with:."Metabolic vulnerabilities of leukemia that spreads to the central nervous system". Link: ID: 827 4734 8072.

10 February 2025, 16.00 CET.Erasmus Hematology Lecture with. Alejandro Sánchez Alvarado, Stowers Institute for Medical Research:. "Stem cells and animal regeneration".Spread the news!.

A new Erasmus Hematology Virtual Lecture series starts Monday, January 27th at 16.00 CET!.We have Gerd Blobel with:."Understanding normal and Dysfunctional gene regulation through the lens of the hemoglobin genes. Check out the fantastic 2025 line up!

A complentary pre-print was posted a few days ago from @tjflemin.bsky.social and @bloodgenes.bsky.social who have reached in a different way very similar conclusions [15/15]

A major challenge for the near future will be to establish inhibitors that either directly target MECOM or promote differentiation by interfering MECOM mediated CEBPA repression. CEBPA expression will be a valuable read-out for MECOM function. [14/15].

Overexpression of 4xPLDLS significantly upregulates CEBPA and induces partial differentiation. The effect size is not as big as when MECOM is depleted, suggesting that there are more mechanisms in play causing CEBPA repression by MECOM. [13/15]

CTBP2 is a co-repressor required for MECOM driven leukemoogenesis (Oncogene EVI1 drives acute myeloid leukemia via a targetable interaction with CTBP2 - PubMed): We developed a 4 X PLDLS construct that blocks CTBP binding to MECOM [12/15]

As part of this paper, we are also releasing a set of new RNA-seq data of a large cohort of patients with 3q26 rearrangements, including classical inv(3)/t(3;3) and variant translocations. These patients show reduced expression of CEBPA. [11/15]

Direct overexpression of CEBPA cDNA in presence of MECOM in 3q26r-MUTZ3 cells bypasses the MECOM-induced block of myeloid differentiation.[10/15]

📷.We derived clones with heterozygous deletion of the +42kb CEBPA enhancer and these do not differentiate upon MECOM loss, indicating that active +42kb enhancers at both alleles are required to bypass the repression imposed by MECOM on CEBPA. [9/15]

CEBPA is a TF that is critical for myeloid development. CEBPA target genes are upregulated upon MECOM k.d. In addition, CEBP motifs are enriched in H3K27ac, RUNX1 and P300 "increased" peaks compared to unchanged peaks. [8/15]

There was no change in 4C interaction between the enhancer and promoter of CEBPA upon MECOM depletion. In addition, we observed small increases in P300 and RUNX1 binding but these were not significant. [7/15].

Using ATAC-seq we found the most significant differentially accessible region upon MECOM loss is a previously described +42kb enhancer of CEBPA. MECOM indeed binds to this region, together with its co-repressor CTBP2. Depletion of MECOM increases H3K27ac at this enhancer. [6/15]

Our model also enabled to study early changes in gene expression using SLAM-seq (3hrs). We mostly found genes upregulated upon MECOM depletion, among which CEBPA. CEBPA is also upregulated upon MECOM shRNA treatment or CRISPR-Cas9 GATA2 enhancer mutation. [5/15]