{"id":239843,"date":"2026-06-27T23:31:46","date_gmt":"2026-06-28T04:31:46","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2026\/06\/single-cell-dissection-of-plasma-cell-clonal-evolution-to-smoldering-multiple-myeloma-after-cd19-car-t-cell-therapy-in-b-cell-acute-lymphoblastic-leukemia"},"modified":"2026-06-27T23:31:46","modified_gmt":"2026-06-28T04:31:46","slug":"single-cell-dissection-of-plasma-cell-clonal-evolution-to-smoldering-multiple-myeloma-after-cd19-car-t-cell-therapy-in-b-cell-acute-lymphoblastic-leukemia","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2026\/06\/single-cell-dissection-of-plasma-cell-clonal-evolution-to-smoldering-multiple-myeloma-after-cd19-car-t-cell-therapy-in-b-cell-acute-lymphoblastic-leukemia","title":{"rendered":"Single-cell dissection of plasma cell clonal evolution to smoldering multiple myeloma after CD19 CAR-T cell therapy in B-cell acute lymphoblastic leukemia"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/single-cell-dissection-of-plasma-cell-clonal-evolution-to-smoldering-multiple-myeloma-after-cd19-car-t-cell-therapy-in-b-cell-acute-lymphoblastic-leukemia2.jpg\"><\/a><\/p>\n<p>Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of B-cell malignancies, achieving deep and durable remissions in patients with B-cell acute lymphoblastic leukemia (B-ALL).<sup><a class=\"\" href=\"https:\/\/haematologica.org\/article\/view\/13160#ref1\">1<\/a><\/sup> Despite remarkable therapeutic successes, rare but clinically significant secondary hematologic malignancies have been reported during CAR-T cell therapy, often driven by lineage switching or clonal selection.<sup><a class=\"\" href=\"https:\/\/haematologica.org\/article\/view\/13160#ref2\">2<\/a><\/sup> Moreover, CAR-T cell therapy drives profound remodeling of the immune microenvironment, and the sustained inflammatory signaling may promote clonal evolution and influence disease progression.<sup><a class=\"\" href=\"https:\/\/haematologica.org\/article\/view\/13160#ref3\">3<\/a><\/sup> High-resolution approaches, such as single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq), enable characterization of transcriptional programs, clonal identity, and temporal dynamics to dissect CAR-T cell therapy-induced clonal evolution and immune remodeling.<sup><a class=\"\" href=\"https:\/\/haematologica.org\/article\/view\/13160#ref4\">4<\/a><\/sup><\/p>\n<p>Here, we report a case of B-ALL with B-cell receptor (BCR) heterogeneity at diagnosis that evolved into smoldering multiple myeloma (SMM) following CD19-targeted CAR-T therapy. The co-occurrence of B-ALL and SMM is exceptionally rare, as it requires malignant clones at distinct stages of B-cell development. This case provides a unique opportunity to dissect how CAR-T cell therapy drives B-lineage clonal evolution and reshapes the immune microenvironment. To this end, bone marrow mononuclear cells (BMMNC) were collected at multiple time points and subjected to longitudinal scRNA-seq and scBCR-seq to track dynamic changes in malignant and immune cell populations, thereby elucidating the mechanisms of clonal evolution and immune remodeling following CAR-T cell therapy. The patient gave informed consent and was enrolled in a clinical trial registered at clinicaltrials.gov (Identifier: NCT00123456).<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of B-cell malignancies, achieving deep and durable remissions in patients with B-cell acute lymphoblastic leukemia (B-ALL).1 Despite remarkable therapeutic successes, rare but clinically significant secondary hematologic malignancies have been reported during CAR-T cell therapy, often driven by lineage switching or clonal selection.2 Moreover, CAR-T [\u2026]<\/p>\n","protected":false},"author":662,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,385],"tags":[],"class_list":["post-239843","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-evolution"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/239843","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/662"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=239843"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/239843\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=239843"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=239843"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=239843"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}