More chronic proliferative diseases (eg, chronic myeloid leukaemia and the early stages of Hodgkin's disease) may involve the expansion of an abnormal, immortalised, clone of pluripotential haemopoietic stem cells or committed haemopoietic progenitor cells that are not autonomous but remain strictly dependent for their proliferation and survival on the presence of exogenous PSF.
More chronic proliferative diseases (eg, chronic myeloid leukaemia and the early stages of Hodgkin's disease) may involve the expansion of an abnormal, immortalised, clone of pluripotential haemopoietic stem cells or committed haemopoietic progenitor cells that are not autonomous but remain strictly dependent for their proliferation and survival on the presence of exogenous PSF.
More chronic proliferative diseases (eg, chronic myeloid leukaemia and the early stages of Hodgkin's disease) may involve the expansion of an abnormal, immortalised, clone of pluripotential haemopoietic stem cells or committed haemopoietic progenitor cells that are not autonomous but remain strictly dependent for their proliferation and survival on the presence of exogenous PSF.
Of special interest was the finding that some cases of Hodgkin's lymphoma and AIL contain clonal rearrangement of the TcR genes, which suggests that in those cases the malignant cells may be of T cell origin.
Cytogenetic analysis of 65 prospectively ascertained non-Hodgkin's lymphomas revealed that the SKI region undergoes nonrandom breakage leading to translocations.
This confirms previous immunohistological data indicating that non-Hodgkin's lymphomas which express the Ki-1 antigen may be of either T-cell or B-cell origin.
Only 5 samples of HD [2 of lymphocytic predominance (HDLP), 2 of mixed cellularity (HDMC), and one of nodular sclerosis type (HDNS)] were found to have both their Ig and T-cell antigen receptor (TcR) genes in the germ-line configuration.
Our findings suggest a close pathogenetic relation between bcl-2 and a large group of non-Hodgkin's lymphomas, both with and without a follicular morphology.
Our studies now show that an intrinsic T cell abnormality exists when HD patients' T cells are stimulated with agonistic MAb that can optimally activate and stimulate IL-2 production in normal control T cells.
Increased expression of bcl-2 after t(14;18) translocations may be a specific marker for B-cell cancers, and demonstration of the protein with use of anti-bcl-2 antibodies could be useful in the diagnosis of many non-Hodgkin's lymphomas.
We can explain these results in at least three ways: first, the neoplastic population could represent less than 1% of the total, thus escaping detection by current techniques; second, the neoplastic population is not lymphoid in nature or is composed of mature cells that do not rearrange Ig and TCR genes and therefore belongs to a true non-B, non-T lineage; third, the pathogenesis of HD is completely different from that of non-Hodgkin's lymphomas (NHL) and does not involve the clonal expansion of a cell frozen at a particular maturative stage as is thought to happen in most NHL.
To study the pathogenesis of Hodgkin's disease (HD), which today remains obscure, we have undertaken a combined experimental approach: determination of TdT and molecular analysis of rearrangements of immunoglobulin heavy chain (IgH), T-cell receptor (TCR) beta chain and the T-cell rearranging gamma (TRG) genes.
We treated 32 patients with Ph1-negative chronic myeloproliferative disorders (CMD) with excessive thrombocytosis with Interferon alpha-2b (IFN alpha-2b): 26 had essential thrombocythaemia, ET (18 previously untreated, eight pretreated); one thrombocythaemia after treatment for Hodgkin's disease (HD); two thrombocythaemia associated with non-Hodgkin's lymphoma (NHL); three stage II idiopathic myelofibrosis (IM).
The bcl-2 gene rearrangement representing t(14:18) chromosomal translocation is the most frequent karyotypic abnormality in non-Hodgkin's lymphomas of follicle center-cell lineage.
When the optimized method was applied to the v-abl-transformed NIH 3T3-, the K 562 CML blast cell line and to nine cases of lowly malignant non-Hodgkin lymphomas it semiquantitatively discriminated the varying amounts of v-abl, bcr/c-abl and c-abl mRNA expressed within these cells.
We postulate that the tumor cells in many cases of HD and some cases of Ki-1-ALC may be derived from immature lymphoid cells by a transformation process that superimposes characteristics of mature activated lymphocytes on these cells.