title: FIP1L1-PDGFRA in chronic eosinophilic leukemia and BCR-ABL1 in chronic myeloid leukemia affect different leukemic cells.
abstract: We investigated genetically affected leukemic cells in FIP1L1-PDGFRA+ chronic eosinophilic leukemia (CEL) and in BCR-ABL1+ chronic myeloid leukemia (CML), two myeloproliferative disorders responsive to imatinib. Fluorescence in situ hybridization specific for BCR-ABL1 and for FIP1L1-PDGFRA was combined with cytomorphology or with lineage-restricted monoclonal antibodies and applied in CML and CEL, respectively. In CEL the amount of FIP1L1-PDGFRA+ cells among CD34+ and CD133+ cells, B and T lymphocytes, and megakaryocytes were within normal ranges. Positivity was found in eosinophils, granulo-monocytes and varying percentages of erythrocytes. In vitro assays with imatinib showed reduced survival of peripheral blood mononuclear cells but no reduction in colony-forming unit growth medium (CFU-GM) growth. In CML the BCR-ABL1 fusion gene was detected in CD34+/CD133+ cells, granulo-monocytes, eosinophils, erythrocytes, megakaryocytes and B-lymphocytes. Growth of both peripheral blood mononuclear cells and CFU-GM was inhibited by imatinib. This study provided evidence for marked differences in the leukemic masses which are targeted by imatinib in CEL or CML, as harboring FIP1L1-PDGFRA or BCR-ABL1.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Crescenzi
authors.forename: A
authors.initials: A
authors.lastname: Chase
authors.forename: R La
authors.initials: RL
authors.lastname: Starza
authors.forename: D
authors.initials: D
authors.lastname: Beacci
authors.forename: V
authors.initials: V
authors.lastname: Rosti
authors.forename: A
authors.initials: A
authors.lastname: Gallì
authors.forename: G
authors.initials: G
authors.lastname: Specchia
authors.forename: M F
authors.initials: MF
authors.lastname: Martelli
authors.forename: P
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: J
authors.initials: J
authors.lastname: Cools
authors.forename: A V
authors.initials: AV
authors.lastname: Jones
authors.forename: N C P
authors.initials: NC
authors.lastname: Cross
authors.forename: P
authors.initials: P
authors.lastname: Marynen
authors.forename: C
authors.initials: C
authors.lastname: Mecucci
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D019070:Cell Lineage; D002908:Chronic Disease; D002999:Clone Cells / Q000201:enzymology; D004351:Drug Resistance; D004804:Eosinophils / Q000201:enzymology; D004912:Erythrocytes / Q000201:enzymology; D016044:Fusion Proteins, bcr-abl / Q000032:analysis* / Q000037:antagonists & inhibitors; D006021:Glycophorins / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006098:Granulocytes / Q000201:enzymology; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000201:enzymology; D008533:Megakaryocytes / Q000201:enzymology; D009000:Monocytes / Q000201:enzymology; D022423:Myeloid Cells / Q000201:enzymology; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000037:antagonists & inhibitors; D010455:Peptides / Q000032:analysis; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis* / Q000037:antagonists & inhibitors; D014410:Tumor Stem Cell Assay; D049951:X Chromosome Inactivation; D039221:mRNA Cleavage and Polyadenylation Factors / Q000032:analysis* / Q000037:antagonists & inhibitors
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D006021:Glycophorins; D006023:Glycoproteins; D015514:Oncogene Proteins, Fusion; C000606023:PROM1 protein, human; D010455:Peptides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D016044:Fusion Proteins, bcr-abl