title: Opposite expression pattern of Src kinase Lyn in acute and chronic haematological malignancies.
abstract: Lck/yes-related novel (Lyn) tyrosine kinase overexpression has been suggested to be important for leukaemic cell growth making it an attractive target for therapy. By contrast, Lyn deficiency was shown to be responsible for a phenotype resembling myeloproliferative neoplasm (MPN) in mice. We aimed to shed more light on Lyn's role in haematological neoplasm and systematically investigated Lyn expression in MPN, acute and chronic leukaemia subtypes (n = 236). On top, B-cell chronic lymphocytic leukaemia (B-CLL) and chronic myeloid leukaemia significantly overexpressed Lyn when compared to de novo acute lymphoblastic leukaemia, de novo acute myeloid leukaemia (AML) and Philadelphia-chromosome-negative myeloproliferative neoplasms (p < 0.001). Most of acute leukaemia subtypes showed a notable down-regulation of Lyn mRNA but anyhow individual cases were labelled for the active form of Lyn protein. Intriguingly, secondary AML evolved in myelodysplastic syndromes revealed almost undetectable Lyn. Overexpression of Lyn in B-CLL was associated with a significant down-regulation of microRNA-337-5p suggesting that aberrant expression of this particular microRNA could be involved in post-transcriptional control of Lyn mRNA fate. We conclude that tyrosine kinase Lyn contributes to the malignant phenotype in certain leukaemia subtypes and therefore attracts targeted therapy.
authors.affiliation: Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Kais
authors.initials: K
authors.lastname: Hussein
authors.forename: Nils
authors.initials: N
authors.lastname: von Neuhoff
authors.forename: Guntram
authors.initials: G
authors.lastname: Büsche
authors.forename: Thomas
authors.initials: T
authors.lastname: Buhr
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Oliver
authors.initials: O
authors.lastname: Bock
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000201:enzymology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D007938:Leukemia / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000201:enzymology / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D053628:Receptors, Thrombopoietin / Q000235:genetics; D055815:Young Adult; D019061:src-Family Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; C544075:Mirn337 microRNA, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases