Biology subjects

Maccaferri, M.

Publications and source records attributed to Maccaferri, M..

3 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↗

bioRxiv2026

Homoeo-alleles of wheat GNI2 fuel grain yields across input environments

Grain yield in wheat is frequently driven by pre-anthesis growth and how carbon is directed to reproductive parts, determining the potential size of the grain-producing sink. However, the genetic mechanisms controlling this carbon allocation remain unclear. In this study we discovered a series of loci in tetraploid and hexaploid wheats that, when combined, confer an average grain yield advantage in hexaploid winter wheat of approx. 5-7% under high-input farming while approx. 10-15% under low-input conditions. The responsible gene is GRAIN NUMBER INCREASE 2 (GNI2), ancestral to its duplicate GNI1, and represented by the homoeo-allelic series GNI-A2, GNI-B2, and GNI-D2. GNI1 and all GNI2 copies additively affect floral growth and fertility by modulating reproductive allocation and harvest index. Herewith, we describe a series of grain yield-relevant GNI2 homoeo-alleles with a proven track record for being beneficial in both high- and low-input environments. Their deployment offers a sustainable pathway to raise global grain yields in the future.

plant biology↗

bioRxiv2018

Yield performance of chromosomally engineered durum wheat-Thinopyrum ponticum recombinant lines in a range of contrasting rain-fed environments across three countries

Introgressions of Thinopyrum ponticum 7AgL chromosome segments, spanning 23%, 28% and 40% of the distal end of durum wheat 7AL arm, were previously shown to contain multiple beneficial gene(s)/QTL for yield-related traits, in addition to effective disease resistance (Lr19, Sr25) and quality (Yp) genes. In the present study, durum wheat near isogenic recombinant lines (NIRLs), harbouring each of the three introgressions, were included for the first time in multi-location field trials, to evaluate general and environment-specific effects of the alien chromatin on 26 yield-related traits. The results from nine different trials across contrasting environments of Italy, Morocco and South Australia over four years revealed that the overall impact of 7AgL introgressions into the tetraploid wheat background did not imply, except in one environment, major yield penalty. The comprehensive effect of the three 7AgL segments on individual yield-contributing traits, resulted in significant increases of biomass m-2 (+9%), spike number m-2 (+13%), grain number m-2 (+11%) and spikelet-1 (+8%), but also in a general, significant decrease of grain weight (-8%). When the separate NIRLs were analysed, each of the three 7AgL segments turned out to be associated with variation of specific yield components. The effects of the 40%-long segment proved to be the most stably expressed across environments and involved significant increases of spike and grain number m-2 (13% and 15%, respectively), grain number spike-1 (10%) and spike fertility index (46%), though accompanied by a significant decrease in thousand grain weight (-23%). In spite of this trade-off between grain number and grain weight, their interplay was such that in four trials, including dryer environments, a grain yield advantage was observed. This evidence, and comparison with the two other NIRLs, substantiates the hypothesized existence of major gene(s)/QTL for grain number in the most proximal 28-40% 7AgL region, exclusive to the 40%-long 7AgL introgression. The present study represents an important validation of the use of chromosomally engineered genetic stocks for durum wheat improvement, targeting not only disease resistance and quality traits but also relevant yield components.

genetics↗