Biology subjects

Malerba, M.

Publications and source records attributed to Malerba, M..

2 recordsLinked to original sources

bioRxiv2026

Therapy-Induced Clonal Selection as a Driver of Response to JAK Inhibitors in Myelofibrosis

Myelofibrosis (MF) originates from the stepwise acquisition of somatic mutations in Hematopoietic Stem and Progenitor Cells (HSPCs). Alongside driver events triggering JAK-STAT pathway hyperactivation, several additional mutations, usually affecting the epigenetic machinery, contribute defining therapeutic response. Specifically, JAK-inhibition (JAKi) relieves MF symptoms but rarely eradicates the neoplastic clone. To elucidate clonal dynamics associated with JAKi, we conducted a longitudinal single-cell proteogenomic study on 6 responders and 6 non-responders MF patients. Mutational analysis revealed that the mutation acquisition order determines JAKi sensitivity. Indeed, driver-only clones are highly sensitive to JAKi, while co-mutated clones persist after treatment. JAKi response is mainly limited to the differentiated myeloid compartment, while mutant HSPCs are often maintained in JAKi-responders. Co-mutated clones may evade JAKi and outcompete other neoplastic cell populations, thus contributing to disease persistence.

cancer biology↗

bioRxiv2021

Long-term experimental evolution decouples size and production costs in Escherichia coli

Body size covaries with population dynamics across lifes domains. Theory holds that metabolism imposes fundamental constraints on the coevolution of size and demography. However, studies of interspecific patterns are confounded by other factors that covary with size and demography, and experimental tests of the causal links remain elusive. Here we leverage a 60,000-generation experiment in which Escherichia coli populations evolved larger cells to examine intraspecific metabolic scaling and correlations with demographic parameters. Metabolic theory successfully predicted the relations among size, metabolism, and maximum population density, with strong support for Damuths law of energy equivalence in this experiment. In contrast, populations of larger cells grew faster than those of smaller cells, contradicting the fundamental assumption that costs of production should increase proportionately with size. The finding that the costs of production are substantially decoupled from size requires re-examining the evolutionary drivers and ecological consequences of biological size more generally.

evolutionary biology↗