Lineage involvement and prognosis in Ph chromosome positive acute lymphoblastic leukaemia

Haferlach et al. (1997) raised an interesting problem concerning the correlation of lineage involvement and prognosis in Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL). By combining May-Grunwald-Giemsa staining with fluorescence in situ hybridization (FISH), the authors provided unequivocal evidence for the presence of BCR/ABL fusion in lymphoid blasts and in granulocytic cells in two patients with a favourable clinical course. These data add to previous studies by Secker-Walker & Craig (1993) who observed a more favourable outcome in Ph+ ALL with multilineage involvement than in similar patients in whom the genetic marker was confined to lymphoid blasts. As Haferlach et al (1997) pointed out, these findings are apparently at variance with a previous study by our group ( Cuneo et al, 1994), describing a poor prognosis in Ph+ ALL with a minor myeloid component, consisting of 5–15% blast cells with morphologic and cytochemical features of the granulocytic lineage. We recently observed a 38-year-old male who presented with Ph+ pre-B ALL, with a minority of myeloid blast cells, who attained late morphologic remission with 13/20 Ph+ metaphases 4 weeks after the start of treatment. In order to study the distribution of the Ph chromosome in the granulocytes and blast cells of this patient we tested a peripheral blood (PB) smear obtained at diagnosis, using the same method as described by Haferlach et al (1997). Hybridization was performed on a slide prepared at diagnosis using a commercial Spectrum Green labelled BCR probe and a Spectrum Orange labelled ABL probe (Vysis, distributed by IL, Milan, Italy). No nuclear counterstaining was used. To ensure better visualization of the BCR probe over the green autofluorescence of the cytoplasm, a blue colour was assigned to the BCR-probe signal by software-assisted image visualization (Genevision 221, Applied Imaging, Nikon Instruments, Florence, Italy). As shown in Fig 1, we could show BCR/ABL fusion in lymphoblasts and myeloblasts (36/40 cells observed) but not in granulocytes (0/18 cells observed). This finding suggests that there is not an absolute correlation between the presence of a minority of myeloid blasts in Ph+ ALL and the presence of BCR/ABL fusion in maturing granulocytes. It is reasonable to assume that the Ph+ stem cell may retain the capability to complete the maturation along the granulocytic pathway in those ALLs with so-called ‘multilineage involvement’, whereas maturation may be blocked at an early stage in those leukaemias with a dual population of blast cells. The presence of a minor myeloid component in Ph+ ALL represents a frequent cause of disagreement in the categorization of ALL ( Loeffler & Gassmann, 1994), prompting some authors to refer to these cases as ‘hybrid acute leukemias’ ( Lo Coco et al, 1989). Interestingly, the outcome in these Ph+ leukaemias with major phenotype deviations was almost uniformly fatal, emphasizing the need for further studies aimed at identifying reproducible prognostic indicators in this disease.