Assessment of peripheral blood and bone marrow cells apoptosis caused by purine analogues in patients with chronic lymphocytic leukemia in correlation with parameters of disease progression.
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with variable clinical course and prognosis. Therefore, the role of prognostic factors is very important, especially for identifying the group of patients who require intensive treatment. The aim of this study was to assess whether the rate of apoptosis caused by purine analogues differs between patients with better or worse prognostic factors. The experiments were preformed in cultures of blood and bone marrow obtained from CLL patients. The cultures were supplemented with cladribine and fludarabine. We determined the percentage of caspase-3-positive cells and the BCL-2/BAX ratio, and subsequently these apoptosis markers were correlated with the expression of ZAP-70 and CD38, lymphocyte counts, lactate dehydrogenase and beta(2)-microglobulin levels and clinical stage according to the Rai classification. The results showed that bone marrow cells are more sensitive to apoptosis caused by purine analogues than cells derived from blood, supporting the idea that these two compartments have different proliferative statuses. The cells from ZAP-70-positive patients seem to enter apoptosis more readily than those from ZAP-70-negative patients; thus, ZAP-70-positive patients are more likely to benefit from treatment with purine analogues.
Podhorecka
Monika
M
Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland. monika.podhorecka@am.lublin.pl
Klimek
Piotr
P
Kowal
Malgorzata
M
Chocholska
Sylwia
S
Bojarska-Junak
Agnieszka
A
Dmoszynska
Anna
A
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016175:B-Lymphocyte Subsets / Q000187:drug effects*; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002908:Chronic Disease; D017338:Cladribine / Q000494:pharmacology*; D018450:Disease Progression; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007945:Leukemia, Lymphoid / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C494826:BAX protein, human; D015415:Biomarkers; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D017338:Cladribine; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D053148:Caspase 3; D014740:Vidarabine; C024352:fludarabine