Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome.
Clonal expansion of leukemic cells is thought to be due to proliferation in excess of apoptosis. To define and compare proliferation and apoptosis between various leukemias and myelodysplastic syndrome (MDS), we measured proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation as surrogate markers for proliferation and caspase 3 activity and annexin V surface binding as surrogate markers for activation of the apoptotic cascade in patients with MDS, chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). We found high proliferation in bone marrow cells from MDS and CMML as measured by PCNA and BrdU incorporation. The lowest level of proliferation was found in CLL. Apoptosis was also highest in MDS and CMML as measured by annexin V and caspase 3 activity. Unexpectedly, we found no significant difference in proliferation in bone marrow CD34+ cells from various leukemias or MDS. Apoptosis was significantly higher in bone marrow CD34+ cells from MDS and CML in chronic phase as compared to CD34+ cells from AML patients. Our results illustrate differences in proliferation and apoptosis between acute and chronic leukemias and MDS. These differences may have diagnostic and therapeutic implications.
Lin
Chung Wu
CW
Department of Hematopathology, MD Anderson Cancer Center, The University of Texas, 1515 Holcombe Blvd., P.O. Box 72, Houston, TX 77030, USA.
Manshouri
Taghi
T
Jilani
Iman
I
Neuberg
Donna
D
Patel
Kunal
K
Kantarjian
Hagop
H
Andreeff
Michael
M
Estrov
Zeev
Z
Beran
Miloslav
M
Keating
Michael
M
Estey
Elihu
E
Albitar
Maher
M
D000208:Acute Disease; D017304:Annexin A5 / Q000378:metabolism; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000473:pathology; D001973:Bromodeoxyuridine / Q000032:analysis / Q000493:pharmacokinetics; D016022:Case-Control Studies; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002908:Chronic Disease; D006801:Humans; D007938:Leukemia / Q000473:pathology* / Q000503:physiopathology; D009190:Myelodysplastic Syndromes / Q000473:pathology* / Q000503:physiopathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011446:Prospective Studies
D017304:Annexin A5; D018952:Antigens, CD34; D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D001973:Bromodeoxyuridine