c-Kit expression in human normal and malignant stem cells prognostic and therapeutic implications

Leukemia Research

Volumn 33, Issue 1, 2009, Pages 5-10

  Hassan, H T ^a  

^a UNIVERSITY OF THE WEST OF SCOTLAND   (United Kingdom)

Author keywords

c Kit; CD117; Drug resistance; Embryonic; Imatinib; Stem cell factor; Stem cells

Indexed keywords

DASATINIB; IMATINIB; PROTEIN TYROSINE KINASE; STEM CELL FACTOR; STEM CELL FACTOR RECEPTOR;

ACUTE MYELOBLASTIC LEUKEMIA; CANCER GROWTH; CANCER STEM CELL; CANCER SURVIVAL; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL RENEWAL; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; DRUG INHIBITION; EDITORIAL; HEMATOLOGIC MALIGNANCY; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; SOLID TUMOR; STEM CELL;

CELL PROLIFERATION; HUMANS; MUTATION; NEOPLASMS; NEOPLASTIC STEM CELLS; PROGNOSIS; PROTO-ONCOGENE PROTEINS C-KIT; STEM CELLS;

EID: 55049139546     PISSN: 01452126     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.leukres.2008.06.011     Document Type: Editorial

References (97)

1. Hassan H.T., and EL-Sheemy M. Adult bone marrow stem cells and their potential in medicine. J Roy Soc Med 97 (2004) 465-471
2. Zhai X., Goodacre J.A., and Hassan H.T. A very small population of cells expressing the CD133 haematopoietic stem cell antigen in normal adult substantia nigra and striatum brain tissues. Haematologica 91 Suppl. 1 (2006) 515-516
3. Galli S.J., Zsebo K.M., and Geissler E.N. The Kit ligand, stem cell factor. Adv Immunol 55 (1994) 1-96
4. Horie K., Takakura K., Tail S., Narimoto K., Noda Y., Nishikawa S., et al. The expression of c-kit protein during oogenesis and early embryonic development. Biol Reprod 45 (1991) 547-552
5. Palmqvist L., Glover C.H., Hsu L., Lu M., Bossen B., Piret J.M., et al. Correlation of murine embryonic stem cell gene expression profiles with functional measures of pluripotency. Stem Cells 23 (2005) 663-680
6. Lu M., Glover C.H., Tien A.H., Humphries R.K., Piret J.M., and Helgason C.D. Involvement of tyrosine kinase signaling in maintaining murine embryonic stem cell functionality. Exp Hematol 35 (2007) 1293-1302
7. Bowie M.B., Kent D.G., Copley M.R., and Eaves C.J. Steel factor responsiveness regulates the high self-renewal phenotype of fetal hematopoietic stem cells. Blood 109 (2007) 5043-5048
8. He X., Gonzalez V., Tsang A., Thompson J., Tsang T.C., and Harris D.T. Differential gene expression profiling of Cd34+CD133+ umbilical cord blood hematopoietic stem progenitor cells. Stem Cells Dev 14 (2005) 188-198
9. Hassan H.T., and Zander A.R. Stem cell factor as a survival and growth factor in human normal and malignant hematopoiesis. Acta Hematol 95 (1996) 257-262
10. Erlandsson A., Larsson J., and Forsberg-Nilsson K. Stem cell factor is a chemotractant and a survival factor for CNS stem cells. Exp Cell Res 301 (2004) 201-210
11. Dolci S., Williams D.E., Ernst M.K., Resnick J.L., Brannan C.I., Lock L.E., et al. Requirement for mast cell growth factor for primordial germ cell survival in culture. Nature 352 (1991) 809-811
12. Yan W., and Suominen J. Toppari stem cell factor protects germ cells from apoptosis in vitro. J Cell Sci 113 (2000) 161-168
13. Hassan H.T., Biermann B., and Zander A.R. Maintenance and expansion of erythropoiesis in human long-term bone marrow cultures in presence of erythropoietin plus stem cell factor and interleukin-3 or interleukin-11. Euro Cytokine Netw 7 (1996) 129-136
14. Ito M., Kawa Y., Ono H., Okura M., Baba T., Kubota Y., et al. Removal of stem cell factor or addition of monoclonal anti-c-kit antibody induces apoptosis in murine melanocyte precursors. J Invest Dermatol 112 (1999) 796-801
15. Matsui J., Wakabayashi T., Asada M., Yoshimatsu K., and Okada M. Stem cell factor/c-kit signaling promotes the survival, migration and capillary tube formation of human umbilical vien endothelial cells. J Biol Chem 279 (2004) 18600-18607
16. Maudiut C., Hamamah S., and Benahmed M. Stem cell factor/c-kit system in spermatogenesis. Hum Reprod Update 5 (1999) 535-545
17. Zhang Z., Zhang R., Joachimiak A., Schlessinger J., and Kong X.P. Crystal structure of human stem cell factor: implications for stem cell factor receptor dimerisation and activation. Proc Natl Acad Sci USA 97 (2000) 77320-77737
18. Langley K.E., Bennett L.G., Wypych J., Yancik S.A., Liu X.D., Westcott K.R., et al. Soluble stem cell factor in human serum. Blood 81 (1993) 656-660
19. Kojima S., Matsuyama T., and Kodera T. Plasma levels and production of soluble stem cell factor by marrow stromal cells in patients with aplastic anaemia. Br J Haematol 99 (1997) 440-446
20. Kitoh T., Ishikawa H., Ishii T., and Nakagawa S. Elevated stem cell factor in the serum of patients with chronic renal failure. Br J Haematol 102 (1998) 1151-1156
21. Sekido Y., Takahashi T., Ueda R., Takahashi M., Suzuki H., Nishida K., et al. Recombinant human stem cell factor mediates chemotaxis of small cell lung cancer cell lines aberrantly expressing the c-kir protooncogene. Cancer Res 53 (1993) 1709-1714
22. Esposito I., Kleeff J., Bischoff S.C., Fischer L., Collecchi P., Lorio M., et al. The stem cell factor-c-Kit system and mast cells in human pancreatic cancer. Lab Invest 82 (2002) 1481-1492
23. Hassan H.T., and Freund M. Stem cell factor protects CD34 positive human myeloid leukaemia cells from chemotherapy-induced apoptosis. In: Pieters R., Kaspers G.J.L., and Veerman A.J.P. (Eds). Drug resistance in leukemia and lymphoma. II. Advances in blood disorders (2007), Harwood Academic Publishers, Switzerland 123-127
24. Ronnstrand L. Signal transduction via the stem cell factor/c-kit. Cell Mol Life Sci 61 (2004) 2535-2548
25. Roskoski Jr. R. Signalling by kit protein-tyrosine kinase-the stem cell factor receptor. Biochem Biophys Res Commun 337 (2005) 1-13
26. Sperger J.M., Chen X., Draper J.E., Antosiewicz C.H., Chon S.B., Brooks J.D., et al. Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumours. Proc Natl Acad Sci USA 100 (2003) 13350-13355
27. Chambers I., and Smith A. Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene 23 (2004) 7150-7160
28. Basahmboo A., Taylor A.H., Samuel K., Panther J.-J., Whetton A.D., and Forrester L.M. The survival of differentiating embryonic stem cells is dependent on the SCF-Kit pathway. J Cell Sci 119 (2006) 3039-3046
29. Ashman L.K. The biology of stem cell factor and its receptor c-kit. Int J Biochem 31 (1999) 1037-1051
30. Majumdar M.K., Thiede M.A., Haynesworth S.E., Bruder S.P., and Gerson S.L. Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages. J Hematother Stem Cell Res 9 (2000) 841-848
31. Fazel S., Cimini M., Chen L., Li S., Angoulvant D., Fedak P., et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest 116 7 (2006) 1865-1877
32. Cimini Fazel S., Zhuo S., Xaymardan M., Fujii H., Weisel R.D., and Li R.K. c-Kit dysfunction impairs myocardial healing after infarction. Circulation 116 11 Suppl. (2007) 177-182
33. Dentelli P., Rosso A., Balsamo A., Colmenares Benedetto S., Zeoli A., Pegoraro M., et al. C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium. Blood 109 (2007) 4264-4271
34. Laurson J., Selden C., Clements M., Mavri-Damelin D., Coward S., Lowdell M., et al. Putative human liver progenitor cells in explanted liver. Cells Tissues Organs 186 (2007) 180-191
35. Dor F.J., Ramirez M.L., Parmar K., Altman E.L., Huang C.A., Down J.D., et al. Primitive hematopoietic cell populations reside in the spleen: studies in the pig, baboon, and human. Exp Hematol 34 11 (2006) 1573-1582
36. Yanagihori H., Oyama N., Nakamura K., and Kaneko F. c-Kit mutations with childhood-onset mastocytosis and genotype-phenotype correlation. J Med Diagnosis 7 (2005) 253-257
37. Sotlar K. Molecular pathological analysis of neoplastic mast cells with regard to the actual WHO classification of mast cell neoplasia. Verh Deutsch Ges Pathol 90 (2006) 227-235
38. Nakata Y., Kimura A., Katoh O., Kawaishi K., Hyodo H., Abe K., et al. c-Kit mutation of extracellular domain in patients with myeloproliferative disorders. Br J Haematol 91 (1995) 661-663
39. Siitonen T., Savolainen G.R., and Koistinen O. Expression of the c-Kit in myeloproliferative disorders and myelodysplastic syndromes. Leukemia 8 (1994) 631-637
40. Bacher U., Haferlach T., kern W., Haferlach C., and Schnittger S. A comparative study of molecular mutations in 381 patients with myelodysplastic syndromes and in 4130 patients with acute myeloid leukemia. Haematologica 92 (2007) 744-752
41. Goemans B.F., Zwaan C.M., Miller M., Zimmermann M., Harlow A., Meshinchi S., et al. Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia 19 (2005) 1536-1542
42. Paschka G., Marcucci A.S., Ruppert K., Mrozek H., Chen R.A., Kittles T., et al. Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): A Cancer and Leukemia Group B Study. J Clin Oncol 24 (2006) 3904-3911
43. Wang Y.Y., Zhou G.B., Yin T., et al. AML 1-ETO and C-Kit mutation/overexpression in t(8;21) leukemia: implication in stepwise leukemogenesis and response to Gleevec. Proc Natl Acad Sci USA 102 (2005) 1104-1109
44. Schnittger S., Kohl T.M., Haferlach T., Kem W., Hiddemann W., Spiekermann K., et al. Kit-D816 mutations in AML1-ETO-positive AML are associated with impaired event-free and overall survival. Blood 107 (2006) 1791-1799
45. Boissel N., Leroy H., Brethon B., Philippe N., de Botton S., Auvrignon A., et al. Incidence and prognostic impact of c-Kit, FLT3 and Ras gene expression in core binding factor acute myeloid leukemia (CBF-AML). Leukemia 20 (2006) 965-970
46. Hongyo T., Li T., Syaifudin M., Baskar R., Ikeda H., Kanakura Y., et al. Specific c-kit mutations in sinonasal natural killer/T-cell lymphoma in China and Japan. Cancer Res 60 (2000) 2345-2347
47. Heinrich M., Blanke C.D., Druker B.J., and Corless C.L. Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of Kit-positive malignancies. J Clin Oncol 20 (2002) 1692-1703
48. Lugli A., West P., Khanlari B., Nikolova Z., and Dirnhofer S. Rare KIT (CD117) expression in multiple myeloma abrogates the usefulness of imatinib mesylate treatment. Virchows Arch 444 (2004) 264-268
49. Hoei-Hansen C.E., Kraggerud S.M., Abeler V.M., Kaem J., Meyts E.R.-D., and Lothe R.A. Ovarian dysgerminomas are characterized by frequent KIT mutations and abundant expression of pluripotency markers. Mol Cancer 6 (2007) 12-16
50. Chilton-MacNeill S., Ho M., Hawkins C., Gassas A., Zielenska M., and Baruchel S. c-Kit expression and mutational analysis in Medulloblastoma. Pediatr Dev Pathol 7 (2004) 498-499
51. Duensing A., Heinrich M., Fletcher C., et al. Biology of gastrointestinal stromal tumors: Kit mutations and beyond. Cancer Invest 22 (2004) 106-116
52. Kim T.W., Lee H., Kang Y.K., Choe M.S., Ryu M.H., Chang H.M., et al. Prognostic significance of c-Kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res 10 (2004) 3076-3081
53. Feinmesser M., Haoern M., Kaganovsky E., Brenner B., Fenig E., Hodak E., et al. c-Kit expression in primary and metastatic Merkel cell carcinoma. Am J Dermatopathol 26 (2004) 458-462
54. Swick B.L., Ravdel L., Fitzpatrick J.E., and Robinson W.A. Merkel cell carcinoma: evaluation of c-Kit (CD117) expression and failure to demonstrate activating mutations in the c-Kit proto-oncogene-implications for treatment with imatinib mesylate. J Cutan Pathol 34 (2007) 324-329
55. Krug L.M., Crapanzano J.P., Azzoli C.G., Miller V.A., Rizvi N., Gomez J., et al. Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-Kit protein: a phase II clinical trial. Cancer 103 (2005) 2126-2131
56. Naeem M., Dahiya M., Clark J.L., Creech S.D., and Alkan S. Analysis of c-Kit protein expression in small-cell lung carcinoma and its implication for prognosis. Hum Pathol 33 (2002) 1182-1187
57. Cohen P.S., Chan J.P., Lipkunskaya M., Lipkunskava M., Biedler J.L., and Seeger R.C. Expression of stem cell factor and c-Kit in human neuroblastoma. Blood 84 (1994) 3465-3472
58. Do I., Araujo E.S., Kalil R.K., Bacchini P., Bertoni F., Unni K.K., et al. Protein expression of Kit and gene mutation of c-Kit and PDGFRs in Ewing sarcomas. Pathol Res Pract 203 (2007) 127-134
59. Gonzalez I., Andreu E.J., Panizo A., Inoges S., Fontalba A., Fernandez-Luna J.L., et al. Imatinib inhibits the proliferation of Ewing tumor cells mediated by the stem cell factor/Kit receptor pathway, and sensitises cells to vincristine and doxorubicin-induced apoptosis. Clin Cancer Res 10 (2004) 751-761
60. Curtin J.A., Busam K., Pinkel D., and Bastian B.C. Somatic activation of KIT in distinct subtypes of Melanoma. J Clin Oncol 26 (2006) 4340-4345
61. Nio Y., Omori H., Hashimoto K., Itakura M., Koike M., Yano Sm., et al. Immunocytochemical expression of receptor-tyrosine kinase c-Kit protein and TGF-beta I in invasive ductal carcinoma of the pancreas. Anticancer Res 25 (2005) 35230-43530
62. Yasuda A., Sawai H., Takahashi H., Ochi N., Matsuo Y., Funahashi H., et al. The stem cell factor/c-Kit receptor pathway enhances proliferation and invasion of pancreatic cancer cells. Mol Cancer 5 (2006) 46-55
63. Schmandt R.E., Broaddus R., Lu K.H., Shvartsman H., Thornton A., Malpica A., et al. Expression of c-ABL, c-Kit and platelet-derived growth factor receptor-beta in ovarian serous carcinoma and normal ovarian surface epithelium. Cancer 98 (2003) 758-764
64. Kemmer K., Corless C.L., Fletcher J.A., McGreevey L., Haley A., and Griffith D. Kit mutations are common in testicular seminomas. Am J Pathol 164 (2004) 305-313
65. William-Payne C., Holden J.A., Chadwick B.E., and Layfield L.J. Dectection of c-Kit exons 11- and 17-activating mutations in testicular seminomas by high-resolution melting amplicon analysis. Mod Pathol 19 (2006) 1164-1169
66. Biermann K., Goke F., Nettersheim D., Eckert D., Zhou H., Kahl P., et al. c-Kit is frequently mutated in bilateral germ cell tumours and down-regulated during progression from intratubular germ cell neoplasia to seminoma. J Pathol 213 (2007) 311-318
67. Hong S.M., Hwang I., Song D.E., Choi J., and Yu E. Clinical and prognostic significances of nuclear and cytoplasmic KIT expressions in extrahepatic bile duct carcinomas. Mod Pathol 20 (2007) 562-569
68. Sammarco I., capurso G., Coppola L., Bonifazi A.P., Cassetta S., Fave G.D., et al. Expression of the proto-oncogene c-Kit in normal and tumor tissues from colorectal carcinoma patients. Int J Colorectal Dis 19 (2004) 545-553
69. Preto A., Moutinho C., Velho S., Oliveria C., Rebocho A.P., Figueiredo J., et al. A subset of colorectal carcinoma expresses c-Kit protein independently of BRAF and/or K-Ras activation. Virchows Arch 450 (2007) 619-626
70. Tsuda H., Tani Y., Weisenberger J., Kitada S., Haseqawa T., Murata T., et al. Frequent KIT and epidermal growth factor receptor over-expression in undifferentiated type breast carcinomas with "stem cell-like" features. Cancer Sci 96 (2005) 333-339
71. Potti A., Ganti A.K., and Tendulkar K. HER-2/neu and CD117 (c-Kit) over-expression in hepatocellular and pancreatic carcinoma. Anticancer Res 23 (2003) 2671-2674
72. Becker G., Schmitt-Graeff A., Ertelt V., Blum H.E., and Allgaier H.-P. CD117 (c-Kit) expression in human hepatocellular carcinoma. Clin Oncol 19 (2007) 204-208
73. Jones C., Rodriquez-Pinilla M., Lambros M., Bax D., Messahel B., Vujanic G.M., et al. c-Kit over-expression without gene amplification and mutation, in paediatric renal tumours. J Clin Pathol 60 (2007) 1226-1231
74. Vercauteren S.M., and Sutherland H.J. CD133 (AC133) expression on AML cells and progenitors. Cytotherapy 3 (2001) 449-459
75. Wuchter C., Ratel R., Spahn G., Schoch C., Harbott J., Schnittger S., et al. U Impact of CD133 (AC133) and CD90 expression analysis for acute leukaemia phenotyping. Haematologica 86 (2001) 154-161
76. Scolnik M.P., Morilla R., de Bracco M.M., Catovsky D., and Matutes E. CD34 and Cd117 are over-expressed in AML and may be valuable to detect minimal residual disease. Leuk Res 26 (2002) 615-619
77. Pietsch T. Paracrine and autocrine growth mechanisms of human stem cell factor (c-kit ligand) in myeloid leukemia. Nouv Rev Fr Hematol 35 (1993) 285-286
78. Ma Y., Cunningham M.E., Wang X., et al. Inhibition of spontaneous receptor phosphorylation by residues in a putative a-helix in the Kit intracellular juxtamembrane region. J Biol Chem 274 (1999) 13399-13402
79. Rassidakis G.Z., Georgakis G.V., Oyarzo M., Younes A., and Medelros L.J. Lack of c-kit (CD117) expression in CD30+ lymphomas and lymphomatoid papulosis. Mod pathol 17 (2004) 946-953
80. Zimpfer A., went T., Tzankov A., Pehrs A.C., Lugli A., Maurer R., et al. Rare expression of KIT (CD117) in lymphomas: a tissue microarray study of 1166 cases. Histopathology 45 (2004) 398-404
81. Slomovitz B.M., Broaddus R.R., Scmandt R., Wu W., Oh J.C., Ramondetta L.M., et al. Expression of imatinib mesylate-targeted kinases in endometrial carcinoma. Gynecol Oncol 95 (2004) 32-36
82. Micke P., Basrai M., Faldum A., Bittinger F., Ronnstrand L., Blaukat A., et al. Characterisdation of c-Kit expression in small cell lung cancer: prognostic and therapeutic implications. Clin Cancer Res 9 (2003) 188-194
83. Raspollini M.R., Amunni G., Villanucci A., Baroni G., Taddei A., and Taddei G.L. c-Kit expression and correlation with chemotherapy resistance in ovarian carcinoma: an immunocytochemical study. Ann Oncol 15 (2004) 594-597
84. Catalano A., Rodilossi S., Rippo M.R., Caprari P., and Procopoi A. Induction of stem cell factor/c-Kit/slug signal transduction in multidrug-resistant malignant mesothelioma cells. J Biol Chem 279 (2004) 46706-46714
85. Buchdunger E., Cioffi C.L., and Law N. Abl protein-tyrosine kinase inhibitor STI-571 inhibits in vitro signal transduction mediated by c-Kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 295 (2000) 139-145
86. Corless C.I., Fletcher J.A., and Heinrich M.C. Biology of gastrointestinal stromal tumours. J Clin Oncol 22 (2004) 3813-3825
87. Piccaluga P.P., Malagola M., Rondoni M., Arpinati M., Paolini S., Candoni A., et al. Imatinib mesylate in the treatment of newly diagnosed or refractory/resistant c-kit positive acute myeloid leukemia. Results of an Italian multicentre phase II study. Haematologica 92 (2007) 1721-1722
88. Coleman R.L., Broaddus R.R., Bodurka D.C., Wolf J.K., Burke T.W., Kavanagh J.J., et al. Phase II trial of imatinib mesylate in patients with recurrent platinum-and taxane-resistant epithelial ovarian and primary peritoneal cancers. Gynecol Oncol 101 (2006) 126-131
89. Alberts D.S., Liu P.Y., Wilczynski S.P., Jang A., Moon J., Ward J.H., et al. Phase II trial of imatinib mesylate in recurrent, biomarker positive ovarian cancer (Southwest Oncology Group Protocol S0211). Int J Gynecol Cancer 17 (2007) 784-788
90. Dy G.K., Miller A.A., Mandrekar S.J., Aubry M.C., Langdon Jr. R.M., Morton R.F., et al. A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small cell lung cancer: a CALGB and NCCTG study. Ann Oncol 16 (2005) 1811-1816
91. Schittenhelm M.M., Shiraga S., Schroeder A., Corbin A.S., Griffith D., Lee F.Y., et al. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res 66 (2006) 473-481
92. Kantarjian H., Pasquini R., Hamerschlak N., Rousselot P., Holowiecki J., Jootar S., et al. Dasatinib or high-dose imatinib for chronic phase CML after failure of first-line imatinib: a randomized phase 2 trial. Blood 109 (2007) 5143-5150
93. Guilhot F., Apperley J., Kim D.W., Bullorsky E.O., Baccarani M., Roboz G.J., et al. Dasatinib induces significant haematologic and cytogentic responses in patients with imatinib-resistant or intolerant CML in accelerated phase. Blood 109 (2007) 4143-4150
94. Cortes J., Rousselot P., Kim D.W., Ritchie E., Hamerschlak N., Coutre S., et al. Dasatinib induces complete haematologic and cytogentic responses in patients with imatinib-resistant or -intolerant CML in blast crisis. Blood 109 (2007) 3207-3213
95. Ottmann O., Dombret H., Martinelli G., Simonsson B., guilhot F., Larson R.A., et al. Dasatinib induces rapid hematologic and cytogentic responses in adult patients with Philadelphia chromosome positive ALL with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood 110 (2007) 2309-2315
96. Brave M., Goodman Y., Kaminskas E., Farrell A., Timmer W., Pope S., et al. Sprycel for CML and Philadelphia chromosome-positive ALL resistant to or intolerant of imatinib mesylate. Clin Cancer Res 14 (2008) 352-359
97. Lu C., and Hassan H.T. Human stem cell factor-antibody [anti-SCF] enhances chemotherapy cytotoxicity in human CD34+ resistant myeloid leukaemia cells. Leuk Res 30 (2006) 296-302