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Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia.

Kaaijk P, Kaspers GJ, Van Wering ER, Broekema GJ, Loonen AH, Hählen K, Schmiegelow K, Janka-Schaub GE, Henze G, Creutzig U, Veerman AJ - Br. J. Cancer (2003)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Hematology/Oncology, VU University Medical Center, Amsterdam, The Netherlands. P.Kaaijk@vumc.nl

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.

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(A) Represented are the percentages of Ki67-positive cells for the different childhood acute leukaemia subgroups. The median value is shown as horizontal bar. The ALL samples taken at initial diagnosis differed significantly from the AML samples taken at initial diagnosis in Ki67 expression (*; P<0.05). iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease. (B) Represented are the percentages of PCNA-positive cells for the different childhood acute leukaemia subgroups. The median value is shown as horizontal bar. No significant differences in PCNA expression in the different subgroups were observed. iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease.
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fig2: (A) Represented are the percentages of Ki67-positive cells for the different childhood acute leukaemia subgroups. The median value is shown as horizontal bar. The ALL samples taken at initial diagnosis differed significantly from the AML samples taken at initial diagnosis in Ki67 expression (*; P<0.05). iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease. (B) Represented are the percentages of PCNA-positive cells for the different childhood acute leukaemia subgroups. The median value is shown as horizontal bar. No significant differences in PCNA expression in the different subgroups were observed. iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease.

Mentions: Comparison of S-phase fractions of peripheral blood (PB) vs bone marrow (BM) samples. Represented are the percentages of cells in S phase for the ALL and AML samples derived from BM or PB. The median value is shown as horizontal bar. Both the initial and relapse ALL samples as well as the initial AML samples derived from BM had a significantly higher S-phase fraction than those derived from PB (*, +, #; P<0.01). The BM-derived ALL samples taken at initial diagnosis differed significantly from those taken at relapsed disease in the S-phase fraction (**; P<0.01). In addition, the BM-derived ALL samples taken at initial diagnosis differed significantly from the initial AML samples (++; P<0.05). iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease.


Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia.

Kaaijk P, Kaspers GJ, Van Wering ER, Broekema GJ, Loonen AH, Hählen K, Schmiegelow K, Janka-Schaub GE, Henze G, Creutzig U, Veerman AJ - Br. J. Cancer (2003)

(A) Represented are the percentages of Ki67-positive cells for the different childhood acute leukaemia subgroups. The median value is shown as horizontal bar. The ALL samples taken at initial diagnosis differed significantly from the AML samples taken at initial diagnosis in Ki67 expression (*; P<0.05). iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease. (B) Represented are the percentages of PCNA-positive cells for the different childhood acute leukaemia subgroups. The median value is shown as horizontal bar. No significant differences in PCNA expression in the different subgroups were observed. iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376358&req=5

fig2: (A) Represented are the percentages of Ki67-positive cells for the different childhood acute leukaemia subgroups. The median value is shown as horizontal bar. The ALL samples taken at initial diagnosis differed significantly from the AML samples taken at initial diagnosis in Ki67 expression (*; P<0.05). iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease. (B) Represented are the percentages of PCNA-positive cells for the different childhood acute leukaemia subgroups. The median value is shown as horizontal bar. No significant differences in PCNA expression in the different subgroups were observed. iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease.
Mentions: Comparison of S-phase fractions of peripheral blood (PB) vs bone marrow (BM) samples. Represented are the percentages of cells in S phase for the ALL and AML samples derived from BM or PB. The median value is shown as horizontal bar. Both the initial and relapse ALL samples as well as the initial AML samples derived from BM had a significantly higher S-phase fraction than those derived from PB (*, +, #; P<0.01). The BM-derived ALL samples taken at initial diagnosis differed significantly from those taken at relapsed disease in the S-phase fraction (**; P<0.01). In addition, the BM-derived ALL samples taken at initial diagnosis differed significantly from the initial AML samples (++; P<0.05). iALL and iAML, samples taken at initial diagnosis; rALL and rAML, samples taken at relapsed disease.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Hematology/Oncology, VU University Medical Center, Amsterdam, The Netherlands. P.Kaaijk@vumc.nl

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.

Show MeSH
Related in: MedlinePlus