Chronic myelogenous leukemia: recent advances.

By R.E. Champlin and OW. Golde C HRONIC myelogenous leukemia (CML) is a hematologic malignancy characterized by excessive growth of myeloid cells and their progenitors.”2 The disease was originally described in 1845 by Craigie,3 Bennett,4 and Virchow,#{176}who noted the classic features of “purulence” of the blood and marked splenomegaly. CML was the first human neoplasm to be associated with a consistent chromosome abnormality, the Philadelphia chromosome (Ph’), which is present in over 90% of cases.6 Cytogenetic studies and glucose-6-phosphate dehydrogenase (G6PD) isoenzyme and analyses7’8 have demonstrated that CML is a clonal disorder of pluripotent hematopoietic stem cells. The Ph’ chromosome or a monoclonal pattern of G6PD isoenzyme expression has been identified in granulocytes, monocytes, macrophages, erythrocytes, megakaryocytes, eosinophils, basophils, and their cornmitted progenitors.9 ‘ Mixed colony-forming cells, CFU-GEMM, also contain the Ph’ chromosome.’4 B lymphocytes and some null cells are also derived from the neoplastic clone.’5”6 It is unclear to what extent T lymphocytes are involved in the malignant process. Peripheral blood T cells responding to lectin have not been reported to contain the Ph’ chromosome and are polyclonal by G6PD analysis.’7 It is possible, however, that small numbers of Ph’-positive T cells are present but cannot be detected among a predominance of normal long-lived T lymphocytes. Recently, several cases of T lymphocyte blast crisis have been reported, suggesting that the disease may involve a pluripotent cell capable of differentiating to T lymphocytes as well as to other myeloid and lymphoid cells.’8”9 The Ph’ chromosome is not present in bone marrow fibroblasts and other mesenchymal tissues.2#{176}