P-gp expression and Rh 123 efflux assay have no impact on survival in Egyptian pediatric acute lymphoblastic leukemia patients.
OBJECTIVE
In a previous work we have studied MDR status in terms of P-glycoprotein (P-gp) expression and Rhodamine 123 efflux assay in Egyptian acute leukemia patients. We have reported results comparable to the literature as regards ANLL both in pediatric and adult cases. However, higher figures were encountered for the functional assay in ALL. As our ALL cases especially in pediatric age group show worse prognosis compared to literature, we hypothesized that the higher percentage of cases with positive Rh123 efflux assay might be a contributing factor.


METHODS
A total of 108 cases were studied including 80 ALL and 28 ANLL. ALL cases included 48 male and 32 female with an age range of 6m to 18 yrs and a median of 7 yrs. ANLL cases included 18 male and 10 female with an age range of 6m to 18 yrs and a median of 8 yrs. P-gp expression was evaluated using 4E3 and UIC2 mAb, analyzed by Coulter XL flow cytometer and expressed as a ratio at a cut off of >or= 1.1 and/or >or= 5% positive cells. For the evaluation of MDR function Rh123 efflux assay using cyclosporine as a blocker and expressed as a ratio at a cutoff of >or= 1.1 and/or >or= 10% positive cells was performed. MDR expression and function were correlated to age, Hb, TLC, CD34 expression, immunophenotype and DNA index in ALL, FAB subtypes in ANLL as well as to CR, DFS and EFS in ALL.


RESULTS
In ALL, P-gp expression was encountered in 26.4% of cases. Positive Rh efflux was reported in 61.5%. No correlation was encountered between neither expression nor functional assay with age, Hb, TLC, CD34 expression or immunophenotype. CR was achieved in 89.8%; neither P-gp expression nor Rh123 efflux had an impact on CR except for Rh123 efflux in T-ALL where a cutoff of 1.25 could predict CR at a total accuracy of 70.6%. DFS was 92.3% while EFS was 72.2% for the whole group. No significant difference was encountered neither between cases expressing or lacking P-gp nor between cases with negative or positive Rh123 efflux assay. In ANLL P-gp expression was encountered in 47.6% of cases, while positive Rh123 efflux assay was encountered in 75% of cases. No correlation as encountered between neither expression nor Rh123 efflux assay and neither age, Hb, TLC, CD34 expression nor FAB subtypes.


CONCLUSIONS
Neither P-gp expression nor Rh123 efflux assay has any impact on survival in pediatric ALL. Rh123 ratio of 1.25 is predictive of CR in TALL.
Kamel
Azza M
AM
The Department of Clinical Pathology, NCI, Cairo University.
El-Sharkawy
Nahla
N
Yassin
Dina
D
Shaaban
Khaled
K
Hussein
Hany
H
Sidhom
Iman
I
Abo El-Naga
Sherif
S
Ameen
Manal
M
El-Hattab
Omer
O
Aly El-Din
Nelly H
NH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000293:Adolescent; D018952:Antigens, CD34 / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D011003:Ploidies; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D020112:Rhodamine 123; D015996:Survival Rate
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018952:Antigens, CD34; D020112:Rhodamine 123