title: Lineage switch and multilineage involvement in two cases of pH chromosome-positive acute leukemia: evidence for a stem cell disease.
abstract: Philadelphia chromosome-positive acute leukemias (Ph+ AL) show variable cytologic features, possibly reflecting heterogeneous stem cell involvement. Morphologic, immunologic and cytogenetic studies were performed in two cases of Ph+ acute lymphoblastic leukemia (ALL) in order to better delineate the clinicobiological features of this cytogenetic subset of AL. Sequential cytoimmunologic studies in patient 1 documented a lineage switch from pro-B ALL with a minor myeloid component at diagnosis to minimally differentiated acute myeloid leukemia (AML) at relapse. In this patient the major breakpoint cluster region (M-bcr) was in a rearranged configuration and all metaphase cells showed t(9;22)(q34;q11), both at diagnosis and at relapse. In patient 2 a diagnosis of Ph+ early T-cell ALL with minor myeloid component was made. In this patient the M-bcr was in a germline configuration. Cytogenetic studies documented the presence of the Ph chromosome in all metaphases from a lymphoid cell population obtained by fine-needle aspiration of an enlarged lymph node, and from a bone marrow cell fraction enriched in granulocyte precursors. This finding suggests multilineage involvement in this patient. Lineage switch and multilineage involvement in two patients suggest that a pluripotent stem cell may be affected rather frequently in patients with Ph+ AL. These findings show that biologically Ph+ AL may resemble chronic myelogenous leukemia blast crisis, since it may originate from an undifferentiated stem cell carrying the t(9;22) translocation.
authors.affiliation: Institute of Hematology, University of Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cuneo
authors.forename: M
authors.initials: M
authors.lastname: Balboni
authors.forename: N
authors.initials: N
authors.lastname: Piva
authors.forename: M G
authors.initials: MG
authors.lastname: Carli
authors.forename: P
authors.initials: P
authors.lastname: Tomasi
authors.forename: R
authors.initials: R
authors.lastname: Previati
authors.forename: M
authors.initials: M
authors.lastname: Negrini
authors.forename: G
authors.initials: G
authors.lastname: Scapoli
authors.forename: R
authors.initials: R
authors.lastname: Spanedda
authors.forename: G
authors.initials: G
authors.lastname: Castoldi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001752:Blast Crisis / Q000175:diagnosis / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D019070:Cell Lineage; D002999:Clone Cells / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage; D003937:Diagnosis, Differential; D018450:Disease Progression; D017809:Fatal Outcome; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000175:diagnosis; D015465:Leukemia, Myeloid, Accelerated Phase / Q000175:diagnosis / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage; D014411:Neoplastic Stem Cells / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000473:pathology; D013713:Teniposide / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D003561:Cytarabine; D014750:Vincristine; D013713:Teniposide; D008942:Mitoxantrone; D015255:Idarubicin