LINEAGE SWITCH AND MULTILINEAGE INVOLVEMENT IN 2 CASES OF PH CHROMOSOME-POSITIVE ACUTE-LEUKEMIA - EVIDENCE FOR A STEM-CELL DISEASE

Philadelphia chromosome-positive acute leukemias (Ph(+) AL) show varia ble cytologic features, possibly reflecting heterogeneous stem cell in volvement. Morphologic, immunologic and cytogenetic studies were perfo rmed in two cases of Ph(+) acute lymphoblastic leukemia (ALL) in order to better delineate the clinicobiological features of this cytogeneti c subset of AL. Sequential cytoimmunologic studies in patient 1 docume nted 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;2 2) (q34;q11), both at diagnosis and at relapse. In patient 2 a diagnos is of Ph(+) early T-cell ALL with minor myeloid component was made. In this patient the M-bcr was in a germline configuration. Cytogenetic s tudies 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 involvem ent in this patient. Lineage switch and multilineage involvement in tw o patients suggest that a pluripotent stem cell may be affected rather frequently in patients with Ph(+) AL. These findings show that biolog ically Ph(+) AL may resemble chronic myelogenous leukemia blast crisis , since it may originate from an undifferentiated stem cell carrying t he t(9;22) translocation.