Background
The diagnosis of blood and bone marrow malignancies relies on detecting excess abnormal hematopoietic stem and progenitor cells (HSPCs) with pathological differentiation. In myelodysplastic syndromes (MDS), abnormal differentiation affects multiple HSPC levels, often with erythroid dysplasia. Currently, most myeloid malignancies are diagnosed through bone marrow (BM) aspirate and biopsy using morphology, FACS, and mutation analysis. Peripheral blood (PB) diagnosis is still limited, as normal circulating HSPC (cHSPC) levels are not well defined. Our recent study (in press, Nature Medicine 2025) analyzed ~3,600 circulating CD34+ cells from 148 healthy individuals using single-cell RNA sequencing (scRNA-seq), defining reference cHSPC frequencies. We propose that deviations from these references can help identify leukemia subtypes. We also present a diagnostic pipeline applied to 73 cytopenia/MDS cases, showing that cHSPC profiling supports MDS diagnosis and suggests possible new MDS subtypes.
HSPCs differentiation from the peripheral blood of healthy individuals :
The current study
We are extending these preliminary results and conducting a multi-center clinical trial aiming at predicting BM results among individuals with cytopenia.
Study objectives
Estimate diagnostic accuracy of scRNAseq of PB CD34pos cells in the diagnosis of cytopenia.
Estimate the accuracy of scRNAseq of PB CD34pos in predicting the IPSS-M score of newly diagnosed patients.
Procedure
The study population are suspected/confirmed MDS MDS/MPN AML cases referred for BM analysis either for diagnosis or risk assessment due to cytopenia.
The final report
The patients report will include
- Diagnosis
- Blast count
- Mutation analysis
- Karyotype Sample report
Sites
The study is currently active in Israel, Taiwan and Canada. Additional sites will soon open in Europe and US.
We are looking for more sites to join us!
Please contact Prof. Liran Shlush (liranshlush3@gmail.com) or Gil Gonen-Yaacovi (gil.gonen-yaacovi@weizmann.ac.il) for more details