共 40 条
Second-Generation Tyrosine Kinase Inhibitors as First-Line Treatment Strategy in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Patients
被引:4
作者:

Breccia, M.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Rome, Italy Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Rome, Italy

Alimena, G.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Rome, Italy Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Rome, Italy
机构:
[1] Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Rome, Italy
关键词:
Chronic myeloid leukemia;
dasatinib;
first-line;
imatinib;
nilotinib;
CHRONIC MYELOGENOUS LEUKEMIA;
ACUTE LYMPHOBLASTIC-LEUKEMIA;
BCR-ABL;
PHARMACOLOGICAL-PROPERTIES;
DASATINIB BMS-354825;
NILOTINIB AMN107;
FOLLOW-UP;
IMATINIB;
CELLS;
MUTAGENESIS;
D O I:
10.2174/156800912800190965
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Recent results of phase II trials which used dasatinib or nilotinib as single agent, or phase III trials comparing second-generation tyrosine kinase inhibitors to imatinib, showed greater potency of these two inhibitors in newly diagnosed chronic myeloid leukemia (CML) patients in chronic phase (CP). In the present review we detail and summarize clinical results of both agents as first-line therapeutic strategy, and also discuss on critical points emerged from the last follow-up of trials comparing new generation tyrosine kinase inhibitors with imatinib. In terms of safety, dasatinib and nilotinib have shown favorable toxicity profile, with peculiar and distinct pattern of adverse events. Based on these results, USA FDA approved both drugs as first-line treatment in newly diagnosed CML: now several therapeutic strategies are available to treat patients at onset of disease. Longer follow-up is however needed to prove the advantages of faster and deeper responses in terms of disease progression compared to imatinib.
引用
收藏
页码:391 / 401
页数:11
相关论文
共 40 条
[1]
SRC: A Century of Science Brought to the Clinic
[J].
Aleshin, Alexey
;
Finn, Richard S.
.
NEOPLASIA,
2010, 12 (08)
:599-607

Aleshin, Alexey
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA

Finn, Richard S.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA
[2]
Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet
[J].
Baccarani, Michele
;
Cortes, Jorge
;
Pane, Fabrizio
;
Niederwieser, Dietger
;
Saglio, Giuseppe
;
Apperley, Jane
;
Cervantes, Francisco
;
Deininger, Michael
;
Gratwohl, Alois
;
Guilhot, Francois
;
Hochhaus, Andreas
;
Horowitz, Mary
;
Hughes, Timothy
;
Kantarjian, Hagop
;
Larson, Richard
;
Radich, Jerald
;
Simonsson, Bengt
;
Silver, Richard T.
;
Goldman, John
;
Hehlmann, Rudiger
.
JOURNAL OF CLINICAL ONCOLOGY,
2009, 27 (35)
:6041-6051

Baccarani, Michele
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Cortes, Jorge
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Pane, Fabrizio
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Niederwieser, Dietger
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Saglio, Giuseppe
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Apperley, Jane
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Cervantes, Francisco
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Deininger, Michael
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Gratwohl, Alois
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Guilhot, Francois
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Hochhaus, Andreas
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Horowitz, Mary
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Hughes, Timothy
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Kantarjian, Hagop
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Larson, Richard
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Radich, Jerald
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Simonsson, Bengt
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Silver, Richard T.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Goldman, John
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy

Hehlmann, Rudiger
论文数: 0 引用数: 0
h-index: 0
机构: Univ Bologna, Dept Hematol Oncol, I-40126 Bologna, Italy
[3]
Comparison of imatinib, mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)-based mutagenesis screen:: high efficacy of drug combinations
[J].
Bradeen, Heather A.
;
Eide, Christopher A.
;
O'Hare, Thomas
;
Johnson, Kara J.
;
Willis, Stephanie G.
;
Lee, Francis Y.
;
Druker, Brian J.
;
Deininger, Michael W.
.
BLOOD,
2006, 108 (07)
:2332-2338

Bradeen, Heather A.
论文数: 0 引用数: 0
h-index: 0
机构: Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA

Eide, Christopher A.
论文数: 0 引用数: 0
h-index: 0
机构: Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA

O'Hare, Thomas
论文数: 0 引用数: 0
h-index: 0
机构: Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA

Johnson, Kara J.
论文数: 0 引用数: 0
h-index: 0
机构: Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA

Willis, Stephanie G.
论文数: 0 引用数: 0
h-index: 0
机构: Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA

Lee, Francis Y.
论文数: 0 引用数: 0
h-index: 0
机构: Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA

Druker, Brian J.
论文数: 0 引用数: 0
h-index: 0
机构: Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA

Deininger, Michael W.
论文数: 0 引用数: 0
h-index: 0
机构: Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA
[4]
Activity and Safety of Dasatinib as Second-Line Treatment or in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Patients
[J].
Breccia, Massimo
;
Alimena, Giuliana
.
BIODRUGS,
2011, 25 (03)
:147-157

Breccia, Massimo
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, I-00161 Rome, Italy Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, I-00161 Rome, Italy

Alimena, Giuliana
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, I-00161 Rome, Italy Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, I-00161 Rome, Italy
[5]
Nilotinib: A second-generation tyrosine kinase inhibitor for chronic myeloid leukemia
[J].
Breccia, Massimo
;
Alimena, Giuliana
.
LEUKEMIA RESEARCH,
2010, 34 (02)
:129-134

Breccia, Massimo
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Biotechnol & Hematol, I-00161 Rome, Italy Univ Roma La Sapienza, Dept Biotechnol & Hematol, I-00161 Rome, Italy

Alimena, Giuliana
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Roma La Sapienza, Dept Biotechnol & Hematol, I-00161 Rome, Italy Univ Roma La Sapienza, Dept Biotechnol & Hematol, I-00161 Rome, Italy
[6]
Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells
[J].
Brendel, C.
;
Scharenberg, C.
;
Dohse, M.
;
Robey, R. W.
;
Bates, S. E.
;
Shukla, S.
;
Ambudkar, S. V.
;
Wang, Y.
;
Wennemuth, G.
;
Burchert, A.
;
Boudriot, U.
;
Neubauer, A.
.
LEUKEMIA,
2007, 21 (06)
:1267-1275

论文数: 引用数:
h-index:
机构:

Scharenberg, C.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Dohse, M.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Robey, R. W.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Bates, S. E.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Shukla, S.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Ambudkar, S. V.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Wang, Y.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Wennemuth, G.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Burchert, A.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Boudriot, U.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany

Neubauer, A.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Marburg, Dept Hematol Oncol & Immunol, D-35033 Marburg, Hessen, Germany
[7]
Dasatinib Is it All in the Dose?
[J].
Condorelli, Fabrizio
;
Genazzani, Armando A.
.
BIODRUGS,
2010, 24 (03)
:157-163

Condorelli, Fabrizio
论文数: 0 引用数: 0
h-index: 0
机构:
DiSCAFF, I-28100 Novara, Italy DiSCAFF, I-28100 Novara, Italy

Genazzani, Armando A.
论文数: 0 引用数: 0
h-index: 0
机构:
DiSCAFF, I-28100 Novara, Italy DiSCAFF, I-28100 Novara, Italy
[8]
Nilotinib As Front-Line Treatment for Patients With Chronic Myeloid Leukemia in Early Chronic Phase
[J].
Cortes, Jorge E.
;
Jones, Dan
;
O'Brien, Susan
;
Jabbour, Elias
;
Konopleva, Marina
;
Ferrajoli, Alessandra
;
Kadia, Tapan
;
Borthakur, Gautam
;
Stigliano, Denise
;
Shan, Jianqin
;
Kantarjian, Hagop
.
JOURNAL OF CLINICAL ONCOLOGY,
2010, 28 (03)
:392-397

Cortes, Jorge E.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Jones, Dan
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

O'Brien, Susan
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Jabbour, Elias
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Konopleva, Marina
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Ferrajoli, Alessandra
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Kadia, Tapan
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Borthakur, Gautam
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Stigliano, Denise
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Shan, Jianqin
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

Kantarjian, Hagop
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
[9]
Results of Dasatinib Therapy in Patients With Early Chronic-Phase Chronic Myeloid Leukemia
[J].
Cortes, Jorge E.
;
Jones, Dan
;
O'Brien, Susan
;
Jabbour, Elias
;
Ravandi, Farhad
;
Koller, Charles
;
Borthakur, Gautam
;
Walker, Brenda
;
Zhao, Weiqiang
;
Shan, Jianqin
;
Kantarjian, Hagop
.
JOURNAL OF CLINICAL ONCOLOGY,
2010, 28 (03)
:398-404

Cortes, Jorge E.
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Jones, Dan
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

O'Brien, Susan
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Jabbour, Elias
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Ravandi, Farhad
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Koller, Charles
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Borthakur, Gautam
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Walker, Brenda
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Zhao, Weiqiang
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Shan, Jianqin
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA

Kantarjian, Hagop
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas MD Anderson Canc Ctr, Dept Leukemia & Hematopathol, Houston, TX 77030 USA
[10]
Nilotinib concentration in cell lines and primary CD34+ chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters
[J].
Davies, A.
;
Jordanides, N. E.
;
Giannoudis, A.
;
Lucas, C. M.
;
Hatziieremia, S.
;
Harris, R. J.
;
Jorgensen, H. G.
;
Holyoake, T. L.
;
Pirmohamed, M.
;
Clark, R. E.
;
Mountford, J. C.
.
LEUKEMIA,
2009, 23 (11)
:1999-2006

Davies, A.
论文数: 0 引用数: 0
h-index: 0
机构:
Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, England Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Jordanides, N. E.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Giannoudis, A.
论文数: 0 引用数: 0
h-index: 0
机构:
Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, England Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Lucas, C. M.
论文数: 0 引用数: 0
h-index: 0
机构:
Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, England Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Hatziieremia, S.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Harris, R. J.
论文数: 0 引用数: 0
h-index: 0
机构:
Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, England Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Jorgensen, H. G.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Holyoake, T. L.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Pirmohamed, M.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Liverpool, Dept Pharmacol & Therapeut, Liverpool L69 3BX, Merseyside, England Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Clark, R. E.
论文数: 0 引用数: 0
h-index: 0
机构:
Royal Liverpool Univ Hosp, Dept Haematol, Liverpool, Merseyside, England Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland

Mountford, J. C.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland Univ Glasgow, Paul OGorman Leukaemia Res Ctr, Fac Med, Div Canc Sci & Mol Pathol,Sect Expt Haematol, Glasgow G12 0NY, Lanark, Scotland