title: Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia.
abstract: Bone marrow and peripheral blood samples from 362 patients with acute lymphoblastic leukaemia (ALL) proliferating cell and 90 patients with acute myeloid leukaemia (AML) were analysed for S-phase fractions, Ki67 antigen, and proliferating cell nuclear antigen expression. The S-phase fractions were correlated with in vitro drug resistance to 15 different anticancer agents. Leukaemia cells isolated from bone marrow had higher S-phase fractions than leukaemia cells isolated from peripheral blood (in initial ALL, median values resp. 6.9 and 2.7%, in initial AML resp. 5.3 and 1.3%; both P<0.01). Relapse ALL samples derived from bone marrow showed increased S-phase fractions (median 9.9%) compared with initial ALL samples (median 6.9%; P<0.01). ALL samples obtained at initial diagnosis showed higher S-phase fractions (median 6.9%) and higher Ki67 expression (median 30%) than initial AML samples (median resp. 5.3 and 14%; both P<0.05). The S-phase fractions were not related to white blood cell count, age, or gender. Within initial ALL, the S-phase fraction correlated significantly but modestly strong (rho=0.3-0.5; P<0.05) with sensitivity to antimetabolites (cytarabine, mercaptopurine, thioguanine), L-asparaginase, teniposide, and vincristine. Similar results were found within subgroups of initial ALL (nonhyperdiploid and common/precursor-B-lineage ALL). In relapsed ALL and AML such correlations were not found. In conclusion, cell proliferation differs between leukaemia subgroups and increased proliferation is associated with increased in vitro sensitivity to several anticancer agents in initial ALL.
authors.affiliation: Department of Pediatric Hematology/Oncology, VU University Medical Center, Amsterdam, The Netherlands. P.Kaaijk@vumc.nl
authors.forename: P
authors.initials: P
authors.lastname: Kaaijk
authors.forename: G J L
authors.initials: GJ
authors.lastname: Kaspers
authors.forename: E R
authors.initials: ER
authors.lastname: Van Wering
authors.forename: G J
authors.initials: GJ
authors.lastname: Broekema
authors.forename: A H
authors.initials: AH
authors.lastname: Loonen
authors.forename: K
authors.initials: K
authors.lastname: Hählen
authors.forename: K
authors.initials: K
authors.lastname: Schmiegelow
authors.forename: G E
authors.initials: GE
authors.lastname: Janka-Schaub
authors.forename: G
authors.initials: G
authors.lastname: Henze
authors.forename: U
authors.initials: U
authors.lastname: Creutzig
authors.forename: A J P
authors.initials: AJ
authors.lastname: Veerman
mesh_terms: D000208:Acute Disease; D002455:Cell Division; D002648:Child; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology*; D016196:S Phase