Andrew Moreno

DocwireNews

A team of investigators from the Weizmann Institute of Science in Rehovot, Israel, is developing a means to detect myelodysplastic syndromes (MDS) based on genetic analysis of circulating hematopoietic stem and progenitor cells (cHSPCs) found in peripheral blood (PB). They presented on their progress at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain.According to the investigators, a method based on circulating CD34+ cells would be a boon to MDS differential diagnosis, clinical evaluation, monitoring, and targeted preventive therapy use. Moreover, compared with bone marrow (BM) aspiration, this &ldquo;noninvasive, specific, and sensitive alternative&hellip;can provide multiple benefits, including earlier detection, better compliance, lower costs, and improved diagnostics.&rdquo;The investigators performed single&#8208;cell RNA sequencing (scRNA&#8208;seq) analysis of PB cHSPCs collected from 150 hematologically healthy persons and from 150 patients with cytopenic or cythemic conditions. Based on 650,000 healthy single CD34+ cell profiles from the 150 healthy individuals, investigators established an atlas of &ldquo;normal&rdquo; cHSPC cell state distributions. They then used the atlas as a reference against which they compared patient-specific models made for the 150 patients.Investigators found they could identify early myeloid malignancies and premalignancies based on how these models deviated in composition from their atlas. In this comparison, they noticed that certain genetic behaviors were linked to particular types of leukemia, specific genes were consistently induced or repressed in disease, and as a patient&rsquo;s disease progressed their cells&rsquo; correlation with the atlas decreased.The findings from scRNA-seq&ndash;based karyotyping were also found to be compatible with BM analysis in the same population.The investigators concluded that their atlas of healthy cHSPC cell states &ldquo;enables high-resolution characterization of myeloid disorders, based on their skewed cell state distributions, compositional-controlled transcriptional variance, abnormal karyotypes, and blast percentage.&rdquo;ReferenceFurer N, Milman O, Rappoport N, Shlush L, Tanay A. MDS diagnosis and risk stratification based on single cell RNA-seq of circulating HSPCs. Abstract S175. Presented at the European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.

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Progress in Detection, Differential Diagnosis of MDS From Peripheral Blood

This noninvasive technique is a potential improvement over bone marrow aspiration for MDS clinical evaluation and monitoring.

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