PMID- 2232849 OWN - NLM STAT- MEDLINE DCOM- 19901204 LR - 20190824 IS - 0145-2126 (Print) IS - 0145-2126 (Linking) VI - 14 IP - 9 DP - 1990 TI - A study of multidrug resistance and cell kinetics in a child with near-haploid acute lymphoblastic leukemia. PG - 771-7 AB - 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 near-haploid 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 multidrug 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 near-haploid leukemia. FAU - Redner, A AU - Redner A AD - Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021. FAU - Hegewisch, S AU - Hegewisch S FAU - Haimi, J AU - Haimi J FAU - Steinherz, P AU - Steinherz P FAU - Jhanwar, S AU - Jhanwar S FAU - Andreeff, M AU - Andreeff M LA - eng GR - CA-38980/CA/NCI NIH HHS/United States GR - CA-41305/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Membrane Glycoproteins) RN - 0 (elastin microfibril interface located protein) RN - CJ0O37KU29 (Verapamil) RN - ZS7284E0ZP (Daunorubicin) SB - IM MH - Cell Cycle MH - Chromosome Aberrations MH - Daunorubicin/pharmacokinetics MH - *Drug Resistance MH - Haplotypes MH - Humans MH - Membrane Glycoproteins/analysis MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics/*pathology MH - Verapamil/pharmacology EDAT- 1990/01/01 00:00 MHDA- 1990/01/01 00:01 CRDT- 1990/01/01 00:00 PHST- 1990/01/01 00:00 [pubmed] PHST- 1990/01/01 00:01 [medline] PHST- 1990/01/01 00:00 [entrez] AID - 10.1016/0145-2126(90)90070-p [doi] PST - ppublish SO - Leuk Res. 1990;14(9):771-7. doi: 10.1016/0145-2126(90)90070-p.