Expression of the human concentrative nucleotide transporter 1 (hCNT1) gene correlates with clinical response in patients affected by Waldenström's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) undergoing a combination treatment with 2-chloro-2′-deoxyadenosine (2-CdA) and Rituximab

C. Rabascio, D. Laszlo, G. Andreola, L. Saronni, D. Radice, L. Rigacci, A. Fabbri, F. Frigeri, L. Calabrese, A. Billio, F. Bertolini, G. Martinelli

Research output: Contribution to journalArticle

Abstract

Purpose: Resistance to nucleoside analogues agents is likely to be multifactorial and could involve a number of mechanisms affecting drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human concentrative nucleoside transporter 1 (hCNT1)-deficient cells display resistance. Experimental design: We applied real-time PCR method to assess the mRNA expression of equilibrative and concentrative nucleoside transporter (hENT1, hCNT1), deoxycytidine and deoxyguanosine kinase (dCK, dGK), 5′-nucleotidase (5′-NT), ribonucleotide reductase catalytic and regulatory (RR1, RR2) subunits in bone marrow cells from 32 patients with Waldenström's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) who received 2CdA-based chemotherapy. Responses to chemotherapy, were then correlated to the expression of these markers. Results: All 32 patients enrolled expressed lower levels of hCNT1 as compared to healthy donors. In univariate analysis, lower expression level of hCNT1 (p = 0.0021) and RR2 (p = 0.02) correlated with response to chemotherapy. In particular, patients with low levels of hCNT1 achieved inferior clinical response. No significant correlation between these genes expression and age, stage of disease was found. This study suggests that nucleotidase expression levels can be used to identify subgroups of WM and SLL patients who will likely respond differently to a 2CdA-based therapy.

Original languageEnglish
Pages (from-to)454-457
Number of pages4
JournalLeukemia Research
Volume34
Issue number4
DOIs
Publication statusPublished - Apr 2010

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Waldenstrom Macroglobulinemia
B-Cell Chronic Lymphocytic Leukemia
Nucleotides
Nucleoside Transport Proteins
Genes
nucleotidase
deoxyguanosine kinase
Drug Therapy
Therapeutics
Deoxycytidine Kinase
Ribonucleotide Reductases
5'-Nucleotidase
Nucleosides
Bone Marrow Cells
2'-deoxyadenosine
Rituximab
Real-Time Polymerase Chain Reaction
Research Design
Tissue Donors
Gene Expression

Keywords

  • 2CdA
  • hCNT1
  • Real-time PCR

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

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title = "Expression of the human concentrative nucleotide transporter 1 (hCNT1) gene correlates with clinical response in patients affected by Waldenstr{\"o}m's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) undergoing a combination treatment with 2-chloro-2′-deoxyadenosine (2-CdA) and Rituximab",
abstract = "Purpose: Resistance to nucleoside analogues agents is likely to be multifactorial and could involve a number of mechanisms affecting drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human concentrative nucleoside transporter 1 (hCNT1)-deficient cells display resistance. Experimental design: We applied real-time PCR method to assess the mRNA expression of equilibrative and concentrative nucleoside transporter (hENT1, hCNT1), deoxycytidine and deoxyguanosine kinase (dCK, dGK), 5′-nucleotidase (5′-NT), ribonucleotide reductase catalytic and regulatory (RR1, RR2) subunits in bone marrow cells from 32 patients with Waldenstr{\"o}m's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) who received 2CdA-based chemotherapy. Responses to chemotherapy, were then correlated to the expression of these markers. Results: All 32 patients enrolled expressed lower levels of hCNT1 as compared to healthy donors. In univariate analysis, lower expression level of hCNT1 (p = 0.0021) and RR2 (p = 0.02) correlated with response to chemotherapy. In particular, patients with low levels of hCNT1 achieved inferior clinical response. No significant correlation between these genes expression and age, stage of disease was found. This study suggests that nucleotidase expression levels can be used to identify subgroups of WM and SLL patients who will likely respond differently to a 2CdA-based therapy.",
keywords = "2CdA, hCNT1, Real-time PCR",
author = "C. Rabascio and D. Laszlo and G. Andreola and L. Saronni and D. Radice and L. Rigacci and A. Fabbri and F. Frigeri and L. Calabrese and A. Billio and F. Bertolini and G. Martinelli",
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T1 - Expression of the human concentrative nucleotide transporter 1 (hCNT1) gene correlates with clinical response in patients affected by Waldenström's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) undergoing a combination treatment with 2-chloro-2′-deoxyadenosine (2-CdA) and Rituximab

AU - Rabascio, C.

AU - Laszlo, D.

AU - Andreola, G.

AU - Saronni, L.

AU - Radice, D.

AU - Rigacci, L.

AU - Fabbri, A.

AU - Frigeri, F.

AU - Calabrese, L.

AU - Billio, A.

AU - Bertolini, F.

AU - Martinelli, G.

PY - 2010/4

Y1 - 2010/4

N2 - Purpose: Resistance to nucleoside analogues agents is likely to be multifactorial and could involve a number of mechanisms affecting drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human concentrative nucleoside transporter 1 (hCNT1)-deficient cells display resistance. Experimental design: We applied real-time PCR method to assess the mRNA expression of equilibrative and concentrative nucleoside transporter (hENT1, hCNT1), deoxycytidine and deoxyguanosine kinase (dCK, dGK), 5′-nucleotidase (5′-NT), ribonucleotide reductase catalytic and regulatory (RR1, RR2) subunits in bone marrow cells from 32 patients with Waldenström's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) who received 2CdA-based chemotherapy. Responses to chemotherapy, were then correlated to the expression of these markers. Results: All 32 patients enrolled expressed lower levels of hCNT1 as compared to healthy donors. In univariate analysis, lower expression level of hCNT1 (p = 0.0021) and RR2 (p = 0.02) correlated with response to chemotherapy. In particular, patients with low levels of hCNT1 achieved inferior clinical response. No significant correlation between these genes expression and age, stage of disease was found. This study suggests that nucleotidase expression levels can be used to identify subgroups of WM and SLL patients who will likely respond differently to a 2CdA-based therapy.

AB - Purpose: Resistance to nucleoside analogues agents is likely to be multifactorial and could involve a number of mechanisms affecting drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human concentrative nucleoside transporter 1 (hCNT1)-deficient cells display resistance. Experimental design: We applied real-time PCR method to assess the mRNA expression of equilibrative and concentrative nucleoside transporter (hENT1, hCNT1), deoxycytidine and deoxyguanosine kinase (dCK, dGK), 5′-nucleotidase (5′-NT), ribonucleotide reductase catalytic and regulatory (RR1, RR2) subunits in bone marrow cells from 32 patients with Waldenström's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) who received 2CdA-based chemotherapy. Responses to chemotherapy, were then correlated to the expression of these markers. Results: All 32 patients enrolled expressed lower levels of hCNT1 as compared to healthy donors. In univariate analysis, lower expression level of hCNT1 (p = 0.0021) and RR2 (p = 0.02) correlated with response to chemotherapy. In particular, patients with low levels of hCNT1 achieved inferior clinical response. No significant correlation between these genes expression and age, stage of disease was found. This study suggests that nucleotidase expression levels can be used to identify subgroups of WM and SLL patients who will likely respond differently to a 2CdA-based therapy.

KW - 2CdA

KW - hCNT1

KW - Real-time PCR

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U2 - 10.1016/j.leukres.2009.07.002

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JO - Leukemia Research

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