New insights into the biology of Philadelphia-chromosome-positive acute lymphoblastic leukaemia using a combination of May-Grünwald-Giemsa staining and fluorescence in situ hybridization techniques at the single cell level.

It is sometimes difficult to discriminate chronic myeloid leukaemia (CML) in lymphatic blast crisis from Ph-chromosome positive acute lymphoblastic leukaemia (ALL). Previous studies have suggested that ALL is restricted to the lymphatic lineage only, whereas CML involves all cell lineages. In four cases of Ph-positive ALL we combined the standard May-Grünwald-Giemsa staining with FISH at the single cell level and were able to demonstrate that > or = 98% of lymphatic blasts carried the Philadelphia chromosome. Erythropoiesis was not involved when this technique was applied. Using immunological identification of single cells (FICTION), we detected the t(9;22) in 100% of CD19-positive B lymphoblasts in all four cases, in some CD3-positive T cells in two patients, and in > or = 98% of CD34-positive precursor cells. However, in two out of four patients the myeloid cell compartment was involved in the malignant transformation, unequivocally demonstrated not only by the combination of MGG and FISH but also by FICTION using the antibodies CD13 and CD33. The observation that both patients with myeloid cell lineage involvement had a myeloid co-expression on their blasts and a better survival supports the concept of a separate, biologically determined subgroup in Ph-positive ALL, leading to further investigations, and individually tailored treatment strategies.