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Vitamin D3 administration and multidrug resistance in acute nonlymphoblastic leukemia
M Petrini1, F Caracciolo, G Carulli
1U.O. Ematologia, Clinica Medica 1, Università di Pisa, Italia.
Abstract:
This article reports preliminary results from a pilot study started in 1986 on patients with acute myeloblastic leukemia treated for several months with low-dose arabinosylcytosine and 1(OH)D3. During treatment or at the time of relapse, a monoblastic component was frequently found. A high percentage of patients were P-170-positive. In 2 patients it was possible to show that blasts, previously P-170-negative, became positive after treatment. In these 2 patients, failure of clinical response to antileukemic therapy was associated with this phenotype. The addition of the revertant drug nicardipine to the previously inactive treatment induced a partial response. Thus, previously reported in vitro observations on the differentiating activity of vitamin D3 metabolites, possible induction of multidrug chemoresistance by differentiating agents and the revertant activity of the Ca++ antagonist nicardipine appear to be confirmed in vivo in the reported patients.
Insights
Low-dose chemotherapy with vitamin D3 metabolites in acute myeloblastic leukemia can induce multidrug resistance. Revertant drug nicardipine showed partial response in P-170-positive patients.
Area of Science:
- Oncology
- Hematology
- Pharmacology
Background:
- Investigating the effects of low-dose arabinosylcytosine and 1(OH)D3 in acute myeloblastic leukemia (AML).
- Assessing the emergence of monoblastic components and P-170 positivity during treatment.
Observation:
- A monoblastic component and P-170 positivity were frequently observed during AML treatment or relapse.
- In two patients, leukemia blasts converted from P-170-negative to P-170-positive post-treatment.
- This P-170-positive phenotype correlated with a lack of clinical response to antileukemic therapy.
Findings:
- Treatment with low-dose arabinosylcytosine and 1(OH)D3 in AML patients can induce multidrug resistance (P-170 positivity).
- The calcium channel blocker nicardipine demonstrated revertant activity, inducing a partial response in patients resistant to standard therapy.
- In vivo confirmation of vitamin D3 metabolite-induced chemoresistance and nicardipine's revertant effects.
Implications:
- Differentiating agents like vitamin D3 may induce chemoresistance in AML, necessitating monitoring for P-170 expression.
- Nicardipine shows potential as an adjunct therapy to overcome chemoresistance in AML.
- These findings highlight the complex interplay between differentiation therapy, drug resistance, and treatment response in AML.