A study of multidrug resistance and cell kinetics in a child with near-haploid acute lymphoblastic leukemia Journal Article

  

Authors:	Redner, A.; Hegewisch, S.; Haimi, J.; Steinherz, P.; Jhanwar, S.; Andreeff, M.
Article Title:	A study of multidrug resistance and cell kinetics in a child with near-haploid acute lymphoblastic leukemia
Abstract:	Marked hypodiploidy is found in a small group of patients with acute lymphoblastic leukemia (ALL) and is associated with very poor prognosis. Cells from a patient with near-haploid ALL (karyotype: 27 XY, DNA index = 0.5) were investigated by multiparameter flow cytometry at relapse and at multiple time-points during reinduction chemotherapy. The cell cycle of these nearhaploid leukemic blasts and their chromatin structure was studied by acridine orange (AO) DNA/RNA flow cytometric assays. Most leukemic cells were in "G0", and no recruitment of the bone marrow cells into the G1 phase of the cell cycle was found during reinduction therapy with high dose cytosine arabinoside. After two cycles of chemotherapy, the patient achieved clinical remission, but persistent haploid cells were identified by flow cytometry and he relapsed after 8 weeks and died after 16.7 weeks. The leukemic blasts expressed very high levels of a 180 kd p-glycoprotein associated with multidrug resistance and daunomycin efflux could be blocked by verapamil. Expression of gp 180 and the verapamil effect on intracellular daunomycin concentration indicate multidrdug resistance. We conclude that cell kinetic quiescence and multidrug resistance may both be factors responsible for the poor prognosis of this patient with near-haploid ALL. Further studies of this patient group should determine if these mechanisms are indeed responsible for the poor prognosis associated with nearhaploid leukemia. © 1990.
Keywords:	adolescent; human cell; prednisone; case report; methotrexate; flow cytometry; cell cycle; haplotypes; combination chemotherapy; cytogenetics; cyclophosphamide; vincristine; drug resistance; acute lymphoblastic leukemia; cell culture; membrane glycoproteins; daunorubicin; asparaginase; chromosome aberrations; verapamil; glycoprotein; multidrug resistance; p-glycoprotein; mercaptopurine; all; cell kinetics; leukemia, lymphocytic, acute; human; male; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title:	Leukemia Research
Volume:	14
Issue:	9
ISSN:	0145-2126
Publisher:	Elsevier Ltd
Date Published:	1990-01-01
Start Page:	771
End Page:	773, 775-777
Language:	English
DOI:	10.1016/0145-2126(90)90070-p
PUBMED:	2232849
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0025123734&doi=10.1016%2f0145-2126%2890%2990070-P&partnerID=40&md5=c92b2e3af0551f6cbfbc5ca0f77cddb7
Notes:	Article -- Export Date: 27 January 2020 -- Source: Scopus

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