The poor response to imatinib observed in CML patients with low OCT-1 activity is not attributable to lower uptake of imatinib into their CD34+ cells.
The functional activity of the organic cation transporter 1 (OCT-1) protein in chronic myeloid leukemia (CML) mononuclear cells (MNCs) is highly predictive of molecular response in imatinib treated patients. Here we investigate whether the MNC OCT-1 activity (OA) provides a surrogate indicator of effective targeting of the more immature CD34(+) cells. While confirming our previous findings that high MNC OA is significantly associated with the achievement of major molecular response (MMR; P = .017), the present studies found no relationship between high CD34(+) OA and the achievement of MMR. Furthermore, no correlation was found between the MNC OA and the CD34(+) OA in matched CML samples. These results suggest that the predictive value of the MNC OA may primarily reflect the effective targeting and subsequent reduction of mature CML cells. Therefore kinase inhibition in these mature cells, and not the CD34(+) cells, may be the key determinant of response in CML.
Engler
Jane R
JR
Division of Haematology, SA Pathology (RAH Campus), Adelaide, Australia.
Frede
Amity
A
Saunders
Verity
V
Zannettino
Andrew
A
White
Deborah L
DL
Hughes
Timothy P
TP
D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000187:drug effects / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000378:metabolism*; D010879:Piperazines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016896:Treatment Outcome
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D027702:Organic Cation Transporter 1; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate