{"id":{"repo_id":"freiburg-diss","oai_identifier":"oai:freidok.uni-freiburg.de:815"},"canonical_url":"https://search.dev.ndltd.org/etd/freiburg-diss/oai:freidok.uni-freiburg.de:815","repository":{"repo_id":"freiburg-diss","name":"University of Freiburg","base_url":"https://freidok.uni-freiburg.de/oai/oai2.php"},"display":{"title":"Investigations on the role of SLP-65 and other B cell signaling proteins in human leukemia","abstract":"SLP-65 is an adaptor protein preferentially expressed in B cells with a central role in BCR and pre-BCR mediated signal transduction. By providing multiple binding sites for other cellular effector molecules it assembles various proteins into one signaling complex. Therefore SLP-65 is involved in the control of different signaling pathways important for B cell development, survival and activation. SLP-65 KO mice demonstrated the critical role of SLP-65 in B cell development. Based on the fact that 5-10 of the SLP-65 KO mice develop pre-B cell leukemia most similar to childhood precursor B cell acute lymphoblastic leukemia, SLP-65 was analyzed in human tumor samples. SLP-65 expression was investigated by RT-PCR, immunoblotting and flow cytometry in 38 samples of precursor B acute lymphoblastic leukemia. In half of the cases SLP-65 protein was reduced or absent. Interestingly, aberrant SLP-65 mRNA splicing was detected in the tumor samples. Alternative exons containing pre-mature stop codons were included in the aberrantly spliced SLP-65 mRNA. These exons were shown to contain pre-mature stop codons leading to nonsense mediated decay of the aberrantly spliced SLP-65 mRNA. In addition, a genetic polymorphism involved in mediating exon recognition was identified. Three of ten patients were deficient for the transcription factor pax-5 involved in regulating SLP-65 expression and one of those patients had aberrant pax-5 mRNA’s lacking the sequences for the transactivation domain. Thus, loss of pax-5 expression could be another possibility to explain the SLP-65 deficiency in addition to aberrant splicing. Our data indicate that a block in pre-B cell differentiation, due to a somatic deficiency in key signaling elements combined with proliferation capacity and active RAG 1/2 enzymes may be the primary cause of pre-B ALL.","abstract_html":"SLP-65 is an adaptor protein preferentially expressed in B cells with a central role in BCR and pre-BCR mediated signal transduction. By providing multiple binding sites for other cellular effector molecules it assembles various proteins into one signaling complex. Therefore SLP-65 is involved in the control of different signaling pathways important for B cell development, survival and activation. SLP-65 KO mice demonstrated the critical role of SLP-65 in B cell development. Based on the fact that 5-10 of the SLP-65 KO mice develop pre-B cell leukemia most similar to childhood precursor B cell acute lymphoblastic leukemia, SLP-65 was analyzed in human tumor samples. SLP-65 expression was investigated by RT-PCR, immunoblotting and flow cytometry in 38 samples of precursor B acute lymphoblastic leukemia. In half of the cases SLP-65 protein was reduced or absent. Interestingly, aberrant SLP-65 mRNA splicing was detected in the tumor samples. Alternative exons containing pre-mature stop codons were included in the aberrantly spliced SLP-65 mRNA. These exons were shown to contain pre-mature stop codons leading to nonsense mediated decay of the aberrantly spliced SLP-65 mRNA. In addition, a genetic polymorphism involved in mediating exon recognition was identified. Three of ten patients were deficient for the transcription factor pax-5 involved in regulating SLP-65 expression and one of those patients had aberrant pax-5 mRNA’s lacking the sequences for the transactivation domain. Thus, loss of pax-5 expression could be another possibility to explain the SLP-65 deficiency in addition to aberrant splicing. Our data indicate that a block in pre-B cell differentiation, due to a somatic deficiency in key signaling elements combined with proliferation capacity and active RAG 1/2 enzymes may be the primary cause of pre-B ALL.","abstract_has_math":false,"creators":["Bossaller, Lukas Friedrich Magnus"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Niemeyer, Charlotte Marie"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T02:21:58Z","subjects":["SLP-65","BLNK","Adaptorprotein","BSAP","pax-5","acute lymphoblastic leukemia","B lymphocyte","tumorsuppressor"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://freidok.uni-freiburg.de/data/815","outbound_label":"Repository record","outbound_source":"source_url"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Niemeyer, Charlotte Marie"]},{"key":"dc:creator","label":"Author","values":["Bossaller, Lukas Friedrich Magnus"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:type","label":"Dc Type","values":["DoctoralThesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["SLP-65","BLNK","Adaptorprotein","BSAP","pax-5","acute lymphoblastic leukemia","B lymphocyte","tumorsuppressor"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["SLP-65 is an adaptor protein preferentially expressed in B cells with a central role in BCR and pre-BCR mediated signal transduction. By providing multiple binding sites for other cellular effector molecules it assembles various proteins into one signaling complex. Therefore SLP-65 is involved in the control of different signaling pathways important for B cell development, survival and activation. SLP-65 KO mice demonstrated the critical role of SLP-65 in B cell development. Based on the fact that 5-10 of the SLP-65 KO mice develop pre-B cell leukemia most similar to childhood precursor B cell acute lymphoblastic leukemia, SLP-65 was analyzed in human tumor samples. SLP-65 expression was investigated by RT-PCR, immunoblotting and flow cytometry in 38 samples of precursor B acute lymphoblastic leukemia. In half of the cases SLP-65 protein was reduced or absent. Interestingly, aberrant SLP-65 mRNA splicing was detected in the tumor samples. Alternative exons containing pre-mature stop codons were included in the aberrantly spliced SLP-65 mRNA. These exons were shown to contain pre-mature stop codons leading to nonsense mediated decay of the aberrantly spliced SLP-65 mRNA. In addition, a genetic polymorphism involved in mediating exon recognition was identified. Three of ten patients were deficient for the transcription factor pax-5 involved in regulating SLP-65 expression and one of those patients had aberrant pax-5 mRNA’s lacking the sequences for the transactivation domain. Thus, loss of pax-5 expression could be another possibility to explain the SLP-65 deficiency in addition to aberrant splicing. Our data indicate that a block in pre-B cell differentiation, due to a somatic deficiency in key signaling elements combined with proliferation capacity and active RAG 1/2 enzymes may be the primary cause of pre-B ALL."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Investigations on the role of SLP-65 and other B cell signaling proteins in human leukemia","Untersuchungen zur Rolle des Adaptorproteins SLP-65 und anderer B-Zell Signaltransduktionsproteine in menschlicher Leukämie"]}]}],"canonical_facts":{"dc:contributor":["Niemeyer, Charlotte Marie"],"dc:creator":["Bossaller, Lukas Friedrich Magnus"],"dc:description.abstract":["SLP-65 is an adaptor protein preferentially expressed in B cells with a central role in BCR and pre-BCR mediated signal transduction. By providing multiple binding sites for other cellular effector molecules it assembles various proteins into one signaling complex. Therefore SLP-65 is involved in the control of different signaling pathways important for B cell development, survival and activation. SLP-65 KO mice demonstrated the critical role of SLP-65 in B cell development. Based on the fact that 5-10 of the SLP-65 KO mice develop pre-B cell leukemia most similar to childhood precursor B cell acute lymphoblastic leukemia, SLP-65 was analyzed in human tumor samples. SLP-65 expression was investigated by RT-PCR, immunoblotting and flow cytometry in 38 samples of precursor B acute lymphoblastic leukemia. In half of the cases SLP-65 protein was reduced or absent. Interestingly, aberrant SLP-65 mRNA splicing was detected in the tumor samples. Alternative exons containing pre-mature stop codons were included in the aberrantly spliced SLP-65 mRNA. These exons were shown to contain pre-mature stop codons leading to nonsense mediated decay of the aberrantly spliced SLP-65 mRNA. In addition, a genetic polymorphism involved in mediating exon recognition was identified. Three of ten patients were deficient for the transcription factor pax-5 involved in regulating SLP-65 expression and one of those patients had aberrant pax-5 mRNA’s lacking the sequences for the transactivation domain. Thus, loss of pax-5 expression could be another possibility to explain the SLP-65 deficiency in addition to aberrant splicing. Our data indicate that a block in pre-B cell differentiation, due to a somatic deficiency in key signaling elements combined with proliferation capacity and active RAG 1/2 enzymes may be the primary cause of pre-B ALL."],"dc:format.medium":["application/pdf"],"dc:subject":["SLP-65","BLNK","Adaptorprotein","BSAP","pax-5","acute lymphoblastic leukemia","B lymphocyte","tumorsuppressor"],"dc:title":["Investigations on the role of SLP-65 and other B cell signaling proteins in human leukemia","Untersuchungen zur Rolle des Adaptorproteins SLP-65 und anderer B-Zell Signaltransduktionsproteine in menschlicher Leukämie"],"dc:type":["DoctoralThesis"]},"updated_at":"2026-07-24T02:21:58Z"}