IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening.

T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoid malignancy with limited treatment options. To discover new treatment targets for T-PLL, we performed high-throughput drug sensitivity screening on 30 primary patient samples ex-vivo. After screening over 2'800 unique compounds, we found T-PLL to be more resistant to most drug classes, including chemotherapeutics, compared to other blood cancers.

Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.

Chronic lymphocytic leukemia is a malignant lymphoproliferative disorder for which primary or acquired drug resistance represents a major challenge. To investigate the underlying molecular mechanisms, we generate a mouse model of ibrutinib resistance, in which, after initial treatment response, relapse under therapy occurrs with an aggressive outgrowth of malignant cells, resembling observations in patients. A comparative analysis of exome, transcriptome and proteome of sorted leukemic murine cells during treatment and after relapse suggests alterations in the proteasome activity as a driver of ibrutinib resistance.

At early stages of heart development, the first and second heart fields are a continuum of lateral head mesoderm-derived, cardiogenic cells.

Pioneering work in the chicken established that the initial development of the heart consists of two stages: the quick assembly of a beating heart, followed by the recruitment of cells from adjacent tissues to deliver the mature in-and outflow tract. Cells to build the primitive heart were dubbed the first heart field (FHF) cells, cells to be recruited later the second heart field (SHF) cells. The current view is that these cells represent distinct, maybe even pre-determined lineages.

Naturally occurring, rostrally conjoining chicken twins attempt to make a forebrain.

Conjoined twinning is a special case of monozygotic, monoamniotic twinning. Human conjoined twinning, and vertebrate conjoined twinning in general, is a very rare phenomenon. It has been suggested that the risk of conjoined twinning increases with some medication and upon assisted reproduction.

Dual Biological Role and Clinical Impact of De Novo Chromatin Activation in Chronic Lymphocytic Leukemia.

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course.