RESUMEN
CD19-targeted chimeric antigen receptor T lymphocytes (CAR-T) has demonstrated a high proportion of complete remission in the treatment of relapsed refractory acute B cell lymphoblastic leukemia (r/r B-ALL). It is of great clinical significance to explore which factors will impact long-term disease-free survival of patients with r/r B-ALL after CAR-T therapy without bridging bone marrow transplantation. Our study found that, in patients with r/r B-ALL without bridging transplantation, the patients' age; infusion dosage; whether they had undergone allo-stem cell transplantation before CAR-T therapy, using CD-19-targeted or CD19/CD22-dual-targeted CAR-T; whether there is fusion gene; tumor burden before therapy; and comorbidity had no significant relationship with their long-term disease-free survival. We found only that CAR-T persistence was highly correlated with patients' long-term disease-free survival. So, we further profiled CAR-T cells using single-cell sequencing and found that there is a specific T cell subset that may be associated with the long-term persistence of CAR-T. Finally, according to the single-cell sequencing results, we established cell production process named PrimeCAR, which shared common signaling pathways with the T cell subset identified. In the preliminary clinical study, prime CAR-Ts yield good persistence in peripheral blood of patients with B-ALL and lymphoma, without observing grade 2 or higher cytokine release syndrome.
RESUMEN
<p><b>OBJECTIVE</b>To analyze linkage disequilibrium of 12 short tandem repeat loci on chromosome X (X-STR) among an ethnic Han population from Guilin, Guangxi, and to study the genetic linkage and haplotype distributions of such loci in 2 linkage groups.</p><p><b>METHODS</b>12 X-STR loci including DXS8378, DXS10159, DXS10162, DXS10164, DXS981, DXS6789, DXS7424, DXS101, DXS7133, GATA165B12, GATA31E08 and DXS7423 were genotyped using an AGCU X12 STR PCR Amplification kit. A total of 119 pedigrees were analyzed for linkage and linkage disequilibrium.</p><p><b>RESULTS</b>Two mutations were found at DXS7424, and 1 mutation was found at DXS10164. A total of 93 haplotypes of DXS10159-DXS10162-DXS10164 were constructed for 261 unrelated males and females, in addition with 167 haplotypes of DXS6789-DXS7424-DXS101-DXS7133. The values of recombination fraction between DXS10159 and DXS10162, DXS10162 and DXS10164, DXS6789 and DXS7424, and DXS7424 and DXS101 were 0.0269, 0.0236, 0.0505 and 0.0438, respectively.</p><p><b>CONCLUSION</b>Linkage disequilibrium of X-STR does not only depend on physical and genetic distances. There was incomplete linkage relationship between loci on DXS10159-DXS1016-DXS10164 and DXS6789-DXS7424-DXS101 linkage groups.</p>
