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

Abstract

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 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 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.

Reticulated platelets in primary and reactive thrombocytosis

“…These data add to previous studies by who observed a more favourable outcome in Ph þ 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 þ ALL with a minor myeloid component, consisting of 5-15% blast cells with morphologic and cytochemical features of the granulocytic lineage.…”

“…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 þ 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.…”

“…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).…”

Reprogramming of primary human philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages

“…Several studies have demonstrated the presence of BCR-ABL1 + myeloid cells in B-ALL patients (23,24). These observations have been attributed to the presence of the BCR-ABL1 translocation in a multipotent progenitor cell, capable of both lymphoid and myeloid differentiation.…”

Therapy-related adult acute lymphoblastic leukemia with t(4;11)(q21; q23): MLL rearrangement, p53 mutation and multilineage involvement

“…The simultaneous analysis of hybridization pattern and cell morphology proved to be an efficient method for the study of lineage involvement in hemopoietic neoplasms 8,9,17 and unequivocally showed that the target stem cell for leukemogenesis in this case of t(4;11) leukemia retained the capability to differentiate in vivo along the lymphoid and granulocytic pathways.…”