Cytogenetics and cell surface marker analysis in CML--1. Prediction of phenotype of acute phase transformation.
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abstract
Thirty-nine patients with Philadelphia chromosome-positive (Ph1) chronic myelocytic leukemia (CML) were monitored using cytofluorometry and cytogenetics. During chronic phase, abnormal populations could be detected using commercially available monoclonal antibodies. Most of these abnormal populations had either an HLA.DR+ or an OKM1+ HLA.DR- phenotype. Thirteen patients progressed to acute phase disease. Five patients with HLA-DR+ abnormal cells during chronic phase showed no clonal evolution detectable using standard cytogenetic techniques and underwent lymphoid transformation. Seven patients with OKM1+-HLA.DR- abnormal cells exhibited chromosomal abnormalities in addition to the Ph1 and progressed to a myeloblastic acute phase. One patient with HLA.DR+ OKM1+ 63D3+ abnormal cells in chronic phase showed clonal evolution and progressed to a myelomonocytic acute phase. These results suggest that cell surface markers on chronic phase cells can be used in conjunction with cytogenetic monitoring to predict the phenotype of cells involved in the acute transformation of CML. B cells (6, 13), but not T cells (18), bearing the Ph1 have been isolated from chronic phase CML patients. Thus cells other than those of myeloid lineage may be involved. Periodic cytogenetic monitoring has been shown to detect clonal evolution (i.e. genetic changes in addition to the PH1) in as many as 75% of patients prior to the acute phase (14, 37). However, neither cytogenetic changes nor morphologic analysis appear to predict the lymphoblastic type of transformation (14). Since fluorescence analysis of cell surface markers has shown reduced numbers of normal cells (28), the identity of the 'abnormal' cells was probed with antibodies recognizing a variety of markers on immature and mature lymphoid and myeloid cells. Not only were significant numbers of abnormal cells detected in the peripheral blood of chronic phase patients, but the phenotype of the abnormal population, in combination with cytogenetic analyses, predicted the type of blasts involved in acute phase disease.
