Nuclear lamin expression reveals a surprisingly high growth fraction in childhood acute lymphoblastic leukemia cells.
In an attempt to better characterize leukemic bone marrow cells of children with ALL in G0/G1, we studied the variation of the nuclear projection area (NPA) during the cell cycle. Approximately half of the increase of the nuclear volume during the cell cycle occurred before DNA synthesis. Next, we assessed by in situ hybridization (ISH) the expression of nuclear envelope type A/C and type B lamins in leukemic lymphoblast and unstimulated as well as stimulated normal peripheral blood mononuclear cells (PBMC). It was found that 82.0 +/- 16.0% of the ALL cells expressed B-type and 5.8 +/- 3.1% A/C-type lamins. The in vitro 3HdT pulse-labeling index (3HdT LI) of ALL cells varied from 1.3 to 16.8%. Of unstimulated PBMC 2.9 and 1.2% expressed lamin type B and A/C, respectively. The 3HdT LI was 0.8%. In conA-stimulated PBMC, the corresponding values were 95.3 and 74.8% and 31.0%, respectively. In view of the current concepts regarding G1 events and regulation of cell proliferation, we considered B-type lamin expression an early marker for the commitment to proliferation and used it for growth fraction (GF) determinations. By this method, a surprisingly high GF was found in ALL cell populations; there was no correlation between GF and the 3HdT LI, as seen in normal cells.
Müller
P R
PR
Laboratory for Clinical and Experimental Research, University of Berne, Switzerland.
Meier
R
R
Hirt
A
A
Bodmer
J J
JJ
Janic
D
D
Leibundgut
K
K
Lüthy
A R
AR
Wagner
H P
HP
D000293:Adolescent; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003208:Concanavalin A / Q000494:pharmacology; D003592:Cytophotometry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D034882:Lamins; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology* / Q000503:physiopathology; D013268:Stimulation, Chemical
D004273:DNA, Neoplasm; D034882:Lamins; D009687:Nuclear Proteins; D003208:Concanavalin A