Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

Abstract

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.

Biology of myelodysplastic syndromes

“…ANLL of the former type appeared to be more common among young individuals and B cell involvement was not detected. In contrast, the latter ANLL involving the pluripotent stem cell occurred in elderly patients with evidence of B cell involvement [147]. Taken together, these observations strongly favor the hypothesis that in MDS and ANLL developing from MDS, the affected target cell is a pluripotent stem cell, while most de novo ANLL without dysplasia arises in a progenitor cell with restrictive expression.…”

Evolution of the Myelodysplastic Syndromes

“…They have shown that in some patients heterozygous for G6PD variants the disease was expressed only in cells with differentiation restricted to the granulocyte-monocyte pathway, while in other patients a progenitor cell was affected, multipotent for at least all myeloid elements. The same group of investigators recently has demonstrated that in a patient whose abnormal clone showed multipotent expression, the ratio of B-A GGPD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukaemic clone) and was significantly different from the 1 : 1 ratio expected (Ferraris et al, 1985). They concluded, therefore, that in this patient the neoplastic event occurred in the pluripotent stem cell, i.e.…”

“…It was also suggested that AML affecting the pluripotent stem cell may have a preceding myelodysplastic phase, while AML arising in a progenitor cell with restricted differentiative expression would not have a myelodysplastic phase. Even the pattern of remission may be different in these two types of AML with the restoration of a nonclonal, presumably normal haematopoiesis in AML, affecting a progenitor cell with restricted differentiative expression, while in AML involving the pluripotent stem cell even complete remission may be clonal, indicating that chemotherapy may destroy only a leukaemic subclone and restore a morphologically and karyotypically normal, but nevertheless clonal preleukaemic state (Jacobson et aI, 1984;Ferraris et al, 1985). We hypothesize that MDS is closely related to the type of AML, that involves the pluripotent stem cell, not only because both disorders arise in the same progenitor cell, but also because they mainly affect elderly individuals.…”