Clonal Rearrangement and Expression of the T Cell Receptor $ Gene and Involvement of the Breakpoint Cluster Region in Blast Crisis of CGL

A case of lymphoid blast crisis of Ph’-positive CGL is described in which the blast cells had an immature T cell phenotype. clonal rearrangement and expression of the T cell receptor fi gene, and a rearrangement of the breakpoint cluster region (bcr) on chromosome 22. This case therefore provides definite evidence for transformation C HRONIC granulocytic leukemia (CGL) originates in a multipotential, hematopoietic stem cell.’’ Progeny of this transformed cell include granulocytic, erythroid, megakaryocytic, and monocytic cells, eosinophils, and B lymphocytes.’4 An involvement of the T cell lineage in Philadelphia (Ph’)-positive CGL has, however, been difficult to establish; attempts to demonstrate the Ph’ chromosome or monoclonality with respect to glucose 6PD in T cells from patients in chronic phase have yielded variable or equivocal results.” Immunophenotyping studies of CGL in blast crisis have shown a preponderance of myeboid and/or B cell precursor phenotypes” with only a few isolated cases of possible T cell lineage involvementY” Similarly, de novo ALL with Ph’ chromosome have common ALL or B cell precursor pheno,3 whereas Ph ‘-positive T-ALL, though is very rare. Two recent cases,”7 one of childhood T lymphoblastic lymphoma and the other of T-ALL, have provided evidence that the ph’ chromosome may arise as a secondary event in the evolution of these disorders. Selective growth advantage of single B cell precursors in blast crisis of CGL has been demonstrated by clonab rearrangements of immunoglobulin genes.”9 The recent availability of molecular probes for the T cell receptor (TCR) fi gene now provides a similar opportunity to explore T cell selection in CGL since this gene rearranges in a similar fashion to immunogbobulin #{176} and is shown to be cbonalby rearranged and transcribed in T cell malignancies.” In addition, the cloning of a DNA probe that specifically recognizes rearrangements in the breakpoint cluster region (bcr) on chromosome 22 in CGL” provides a new and unique molecular marker to analyze particular cell types including T cells for their involvement in CGL. We recently identified a rare case of blast crisis of Ph’ CGL in which the blast cells had the composite phenotype of thymic leukemia cells (cf T-ALL). We report here the detailed immunophenotype of this case and results for probing for rearrangement and expression of TCR / gene and also for involvement of bcr. involving a common myeloid-T lineage progenitor. penetrance of the Ph’ molecular alteration into the T cell lineage, and clonal selection in blast crisis at the level of a committed T lineage precursor. C 1986 by Grune & Stratton, Inc.