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  • Title: Lineage switch and multilineage involvement in two cases of pH chromosome-positive acute leukemia: evidence for a stem cell disease.
    Author: Cuneo A, Balboni M, Piva N, Carli MG, Tomasi P, Previati R, Negrini M, Scapoli G, Spanedda R, Castoldi G.
    Journal: Haematologica; 1994; 79(1):76-82. PubMed ID: 15378954.
    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.
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