Relationship between DNA Index and Cellular Drug Resistance in Children with Newly Diagnosed Acute Lymphoblastic Leukemia.

Leukemic cell ploidy is known risk factor in childhood leukemia. Hypodiploidy (DNA index < 1.00 or chromosome number <46) was shown as adverse prognostic factor in many study. The cause of poor prognosis is not known. Cellular drug resistance might provide important information on this subject. In this study, we want to evaluate LC50 (lethal concentration to 50% of cells) values of 7 different drugs in 34 newly diagnosed patient and compare those of hypodiploid with nonhypodiploid patients. DNA index was determined by flowcytometric analysis of cellular DNA content and cell cycle distribution with Coulter EPICS XL-MCL system on propidium iodide stained cells. DNA index was defined as the modal DNA content of leukemic cells compared with that of reference normal lymphocytes. Patients were divided in hypodiploid (DNA index < 1.00) and nonhypodiploid (DNA index ≥ 1.00)

We carried out in vitro tests with a 4-day culture and a methyl-thiazol- tetrazolium (MTT) assay on bone morrow samples of patients to get LC50 values for 7 different classes of drugs(PRD, prednisolon; DEXA, dexamethasone; VCR, vincristine; ASP, l-asparaginase; ADR, adriamisin; DNR, daunorubisin; ARA-C, cytosine arabinoside) commonly used in treatment of ALL. Eigth patients (23.5%) were belong to hypodiploid group whereas 26 patiens (76.5%) were included in nonhypodiploid group. Sex and age distribution were not different between groups. MTT test were succesfully performed in 7 out 8 hypodiploid patient for each drug. Median LC50 values for PRD and ARA-C were similar. Median LC50 values of hypodiploid group for DEXA, VCR, ASP and ADR were 5.4, 3.5, 5.9 and 3.4 fold higher than those of nonhypodiploid group and were found to be statistically significant. Only the median LC50 value of hypodiploid group for DNR were lower than that of the nonhypodiploid group (p <0.046).

In conclusion, cellular drug resistance might provide important information in relation to poor prognosis of hypodiploid ALL patients. It might also help to individualize the treatment according to drug resistance profiles. Further studies, large study groups and long-term follow-up are needed to confirm these results.