Investigation of clonal involvement of myeloid cells in Philadelphia-positive and high hyperdiploid acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) with a high hyperdiploid clone has a goo d prognosis far both childhood and adult patients while patients with Phila delphia-positive (Ph) ALL do badly at all age groups. It has been suggested that different responses to treatment might be related to the cell of orig in of the leukemia with 'stem cell' cases responding less well than those a rising in a lymphoid committed progenitor cell. The clonal involvement of d ifferent cell lineages in 12 patients with acute lymphoblastic leukemia has been examined by applying fluorescence in situ hybridization (FISH) to det ect chromosomal abnormalities in bone marrow cells previously identified by morphology and/or immunology. The karyotype of the malignant clone was eit her high hyperdiploid or Philadelphia translocation (Ph) positive with a br eakpoint in the minor breakpoint cluster region of the BCR gene (m-BCR) or in the major breakpoint cluster region of the BCR gene (M-BCR). The high hy perdiploid clone, in each case, was found in cells of the B-lymphoid (CD19( +)) lineage but not in T cells (CD3(+)) or in cells of the myeloid (CD13(+) ) or erythroid (glycophorin A(+)) lineages, indicative of a lymphoid commit ted progenitor cell. Heterogeneity of lineage involvement was found in PhALL: the m-BCR Ph+ clone was found in lymphoid/blast cells but not in neutr ophils or eosinophils. In contrast both M-BCR Ph+ clones were detected in m yeloid as well as lymphoid lineages, indicative of a stem cell origin.