Expression of wild-type p53 and Bcl-2 family genes oscillates with recurrent remission and relapse in an unusual case of low-grade lymphoma.
Downregulation of apoptosis has been proposed as a mechanism of clonal expansion in low-grade B cell neoplasms. We have previously described an unusual case of CD5+ B cell lymphoma characterized by cycles of leukemic phase alternating with spontaneous remission. In the present study, we examined the involvement of apoptosis-related proteins in the progression of this cyclic lymphoma ex vivo. During the leukemic phases, the clonal cells were activated blasts expressing elevated levels of wild-type (wt) p53, Bcl-2, Bcl-x(L), and Bax, while Bak expression increased during the decline of lymphocytosis. Bax heterodimerized with Bcl-2 but not with Bcl-x(L). The anti-apoptotic Bcl-2/Bax heterodimers peaked during early leukemic phases and declined during regression. The elevation in Bcl-2, Bcl-x(L) and Bax expression during early leukemic phases seems to result from cell activation since a similar increase was induced by activating the remission phase leukemic cells in culture. The data suggest that wt p53, Bcl-x(L), and Bcl-2/Bax heterodimers support the accumulation of activated leukemic cells during the leukemic phases, while Bax and Bak may be involved in their decline during regression.
Aizman
I
I
Institute of Hematology, Chaim Sheba Medical Center Tel-Hashomer, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Many
A
A
Peller
S
S
Ramot
B
B
Kaufmann
Y
Y
D000208:Acute Disease; D017209:Apoptosis; D001854:Bone Marrow Cells; D018956:CD5 Antigens; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D019281:Dimerization; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007938:Leukemia / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism*; D012008:Recurrence; D012075:Remission, Spontaneous; D017154:Stromal Cells; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D018956:CD5 Antigens; D016207:Cytokines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein