Murine BCL-1B-cell leukemia thus provides a unique model of disseminated B-lineage leukemia to evaluate the antileukemic efficacy of anti-CD19 immunotoxins.
It was shown that bcl-2 gene rearrangements were exclusively confined to centroblastic-centrocytic lymphomas. bcl-1 rearrangements were found in two cases of chronic lymphocytic leukaemia.
In conclusion, the bcl-1 locus rearranges in only about 4% of B-cell CLLs and NHLs, is predominantly rearranged in low-grade B-cell neoplasms, and does not appear to be preferentially associated with those occasional CLLs and low-grade NHLs displaying clinical aggressiveness, advanced clinical stage, or large cell transformation (Richter's syndrome).
Previous studies have suggested an association between t(11;14) chromosomal translocations and bcl-1 rearrangement in centrocytic and related intermediate lymphocytic lymphomas.
All samples showed JH rearrangement, and three samples (two diffuse small lymphocytic lymphomas and one diffuse large cell lymphoma probably transformed from a diffuse small lymphocytic lymphoma) demonstrated rearranged bcl-1 sequences.
The patients with chronic lymphocytic leukaemia (CLL) also showed findings indicating a distinctive disease entity: a CD5+CD10-IgD+ phenotype and lack of PRAD1 over-expression.
Among chronic lymphoproliferative disorders other than MCL, only 1 atypical chronic lymphocytic leukemia (CLL) with a t(11;14) translocation and bcl-1 rearrangement and the 2 hairy cell leukemias (HCLs) analyzed showed upregulation of PRAD-1 gene.
The 11q13 breakpoint region of t(11;14) (q13;q32), translocated to the Ig heavy chain locus at 14q32, has been designated as BCL-1 for B-cell leukemia/lymphoma-1, but the nature of the transcriptional unit has long remained unclear.
Each of the bcl-1-rearranged cases showed high levels of cyclin D1 expression, whereas no expression was detected in RNA from samples of B-cell CLL, T-cell prolymphocytic leukemia, or acute nonlymphocytic leukemia which lacked bcl-1 or cyclin D1 rearrangement.
Although initial reports on small panels of cases had suggested a role for Bcl-1 and Bcl-2 oncogene activation in B-CLL, later investigations failed to confirm these data.
Polymerase chain reaction was performed using a JH consensus primer and specific primers for chromosome II in the MTC region. bcl-1 rearrangement was identified by Southern blot in the MTC in nine (43%) MCLs and in the p94PS region in the CLL.
They also suggest that Ag may play a role in the clonal selection of some of these isotype-switched leukemic cells, but bcl-1 and bcl-2 oncogene rearrangements and p53 tumor suppressor gene mutation are not associated with the pathogenesis of isotype-switched CLLs.
We arrived at the following conclusions: (a) FISH with this BCL1 YAC probe is an efficient method for the detection of the t(11;14) and of the corresponding involvement of the BCL1 locus in this lymphoproliferative disorder; (b) the majority of BCL1-positive atypical CLLs by French-American-British criteria may carry 13q14 deletions; (c) the recognition of this cytogenetic subset of atypical CLL, sharing some immunological and cytogenetic features with mantle cell lymphoma, may be important, because these patients usually present isolated peripheral blood and marrow lymphocytosis, with or without mild to moderate spleen involvement, and may require early cytotoxic treatment.
Thus this rearrangement appears to be very rare in B-CLL and its finding should lead to a careful search for the characteristic features of MZL, namely, morphology, the expression of CD5 without CD23, high density monotypic SIg, together with t(11;14) and/or bcl-1/IgH rearrangement.
In contrast, one case of small lymphocytic lymphoma/chronic lymphocytic leukemia (1/18; 6%) and one case of hairy cell leukemia (1/5; 20%) expressed cyclin D1 protein.
Both methods were applied to isolate VH genes from murine B cell lymphoma (A20 and BCL1), myeloma (NS1) and hybridoma (SP6) cell lines and from freshly isolated human chronic lymphocytic leukemia and lymphoma cells.
We report here a small deletion in the 3'-untranslated portion of the cyclin D1 gene in leukemia cells of a patient diagnosed with B-chronic lymphocytic leukemia (CLL), associated with overexpression of the corresponding cyclin D1 mRNA.