Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma

Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Methods:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL.We identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell subtype.Subsequently,we identified cell markers,including a series of genes associated with immune escape and drug resistance.In addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL samples.Results:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B cells.The drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival promotion.Type III B cells closely communicate with other cells.The key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic value.Conclusion:This study investigated potential immune escape and drug resistance mechanisms in MCL.The results may guide individualized treatment and promote the development of therapeutic drugs.

An addition of medium-dose ATG to conditioning regimens favours the long-term survival of patients with allogeneic hematopoietic stem cell transplantation

Long-term survival of 116 leukemia/MDS patients received allo-SCT conditioned by a regimen with ATG-F or without ATG-F was analysed, together with the impact of ATG-F on the long-term survival, GVHD and disease relapse. Seventy patients received an ATG-F containing conditioning regimen FBCA, and 46 patients received a non-ATG-F FBC regimen. The FBCA regimen was associated with a 5-year survival of 65.4% in the complete HLA-matched group and 39.3% in the HLA-mismatched group. The difference between the two groups was significant (P = 0.012). For the FBC conditioning regimen, the 5-year overall survival of HLA-matched patients and the HLA-mismatched patients was 34.2% and 24.2% respectively (P = 0.216). The incidence of cGVHD was 32.9% and 83.6% in the FBCA and FBC condition regimen group respectively. Only 2.9% of the cases showed extensive cGVHD in the FBCA group while it was 69.4% in the FBC group (P = 0.00). Multivariate analysis indicated that relapse was related to the disease status and HLA typing, but unrelated to the conditioning regimens whether or not ATG-F was used (HR 0.54, P = 0.109). We conclude that the addition of ATG-F to conditioning regimen favours the longterm survival of allo-SCT.