title: Large granular lymphocytosis during dasatinib therapy.
abstract: Dasatinib is a second generation tyrosine kinase inhibitor (TKI) approved for clinical use in patients with imatinib-resistant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Large granular lymphocytes (LGLs) are medium to large cells with eccentric nuclei and abundant cytoplasm with coarse azurophilic granules. LGL lymphocytosis is caused by a proliferation of cytotoxic (CD8+) T cells and/or NK cells. In a proportion of CML and Ph(+) ALL patients, there is a significant expansion of LGLs during dasatinib therapy. LGL lymphocytosis is seen in some cases with fevers, colitis, and pleural effusions (PE), suggesting an aberrant immune response mediated by these LGLs. LGLs may participate in the elimination of the residual leukemic cells, and LGL clonal expansion is associated with excellent, long-lasting therapy responses in dasatinib-treated patients. For a more comprehensive analysis, we analyzed the morphologic, phenotypic, clinical, and functional features of the LGL subsets amplified in vivo during dasatinib therapy.
authors.affiliation: Department of Hematology; the First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital; Nanjing, PR China.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Qiu
authors.affiliation: Department of Hematology; the First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital; Nanjing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Hematology; the First Affiliated Hospital of Nanjing Medical University; Jiangsu Province Hospital; Nanjing, PR China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003092:Colitis / Q000139:chemically induced; D000069439:Dasatinib; D065627:Familial Primary Pulmonary Hypertension / Q000139:chemically induced; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D008218:Lymphocytosis / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D010996:Pleural Effusion / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000069439:Dasatinib
keywords: dasatinib; large granular lymphocyte; pleural effusion; response; tyrosine kinase inhibitor