New molecular concepts and targets in acute myeloid leukemia

Current Opinion in Hematology

Volumn 15, Issue 2, 2008, Pages 82-87

  Buzzai, Monica ^a   Licht, Jonathan D ^a,b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b Division of Hematology/Oncology   (United States)

Author keywords

Acute myeloid leukemia; Cell surface antigens; Hematopoietic stem cells; Histone methyltransferase; HOX genes; Leukemic stem cells

Indexed keywords

HOX PROTEIN; MEMBRANE ANTIGEN; MOLECULAR MARKER; TRANSCRIPTION FACTOR CDX2;

ACUTE GRANULOCYTIC LEUKEMIA; CELL RENEWAL; CELL SURVIVAL; CELL TRANSFORMATION; CHROMATIN; GENE EXPRESSION; HEMATOPOIETIC STEM CELL; HUMAN; PRIORITY JOURNAL; REVIEW; STEM CELL;

ANTIBODIES, MONOCLONAL; GENES, HOMEOBOX; HEMATOPOIETIC STEM CELLS; HUMANS; IMMUNOCONJUGATES; LEUKEMIA, MYELOID, ACUTE; NEOPLASM, RESIDUAL; RECEPTORS, IMMUNOLOGIC; RECEPTORS, INTERLEUKIN-3;

EID: 40049103766     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/MOH.0b013e3282f3ded0     Document Type: Review

References (51)

1. -/HLA-DR. Blood 1998; 92:4325-4335.
2. Dick JE. Complexity of the human acute myeloid leukemia stem cell compartment: implications for therapy. Biol Blood Marrow Transplant 2005; 11:9-11.
3. Huntly BJ, Gilliland DG. Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 2005; 5:311-321.
4. Cozzio A, Passegue E, Ayton PM, et al. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 2003; 17:3029-3035.
5. Huntly BJ, Shigematsu H, Deguchi K, et al. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 2004; 6:587-596.
6. Krivtsov AV, Twomey D, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 2006; 442:818-822.
7. Stone RM, O'Donnell MR, Sekeres MA. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program 2004:98-117.
8. Lowenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program 2003:82-101.
9. Feller N, van der Pol MA, van Stijn A, et al. MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia. Leukemia 2004; 18:1380-1390.
10. - leukemic progenitors. Leukemia 1999; 13:1513-1518.
11. Feller N, Schuurhuis GJ, van der Pol MA, et al. High percentage of CD34-positive cells in autologous AML peripheral blood stem cell products reflects inadequate in vivo purging and low chemotherapeutic toxicity in a subgroup of patients with poor clinical outcome. Leukemia 2003; 17:68-75.
12. Deshpande AJ, Cusan M, Rawat VP, et al. Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia. Cancer Cell 2006; 10:363-374.
13. Jordan CT, Upchurch D, Szilvassy SJ, et al. The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells. Leukemia 2000; 14:1777-1784.
14. 388IL3) prolongs disease-free survival of leukemic immunocompromised mice. Leukemia 2003; 17:155-159.
15. Frankel AE, McCubrey JA, Miller MS, et al. Diphtheria toxin fused to human interleukin-3 is toxic to blasts from patients with myeloid leukemias. Leukemia 2000; 14:576-585.
16. Feuring-Buske M, Frankel AE, Alexander RL, et al. A diphtheria toxin-interleukin 3 fusion protein is cytotoxic to primitive acute myeloid leukemia progenitors but spares normal progenitors. Cancer Res 2002; 62:1730-1736.
17. Hogge DE, Yalcintepe L, Wong SH, et al. Variant diphtheria toxin-interleukin-3 fusion proteins with increased receptor affinity have enhanced cytotoxicity against acute myeloid leukemia progenitors. Clin Cancer Res 2006; 12:1284-1291.
18. Yalcintepe L, Frankel AE, Hogge DE. Expression of interleukin-3 receptor subunits on defined subpopulations of acute myeloid leukemia blasts predicts the cytotoxicity of diphtheria toxin interleukin-3 fusion protein against malignant progenitors that engraft in immunodeficient mice. Blood 2006; 108:3530-3537.
19. Du X, Ho M, Pastan I. New immunotoxins targeting CD123, a stem cell antigen on acute myeloid leukemia cells. J Immunother (1997) 2007; 30:607-613.
20. van der Velden VH, Schoch C, Langerak AW, et al. Low frequency of reverse transcription polymerase chain reaction-detectable chromosome aberrations in relapsed acute myeloid leukaemia: implications for detection of minimal residual disease. Br J Haematol 2001; 113:1082-1083.
21. Linenberger ML. CD33-directed therapy with gemtuzumab ozogamicin in acute myeloid leukemia: progress in understanding cytotoxicity and potential mechanisms of drug resistance. Leukemia 2005; 19:176-182.
22. + AML stem cells. Eur J Clin Invest 2007; 37:73-82.
23. Larson RA, Sievers EL, Stadtmauer EA, et al. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 2005; 104:1442-1452.
24. Walter RB, Gooley TA, van der Velden VH, et al. CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy. Blood 2007; 109:4168-4170.
25. Bakker AB, van den Oudenrijn S, Bakker AQ, et al. C-type lectin-like molecule-1: a novel myeloid cell surface marker associated with acute myeloid leukemia. Cancer Res 2004; 64:8443-8450.
26. - cells from patients in complete remission express the CLL-1 antigen. CLL-1 can be used to target the LSC population at diagnosis.
27. - stem cell compartment in acute myeloid leukemia allows to distinguish the malignant from the normal stem cell compartment both at diagnosis and in remission. Leukemia 2007; 21:1700-1707.
28. Hosen N, Park CY, Tatsumi N, et al. CD96 is a leukemic stem cell-specific marker in human acute myeloid leukaemia. Proc Natl Acad Sci USA 2007; 104:11008-11013.
29. Avecilla ST, Hattori K, Heissig B, et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med 2004; 10:64-71.
30. Tavor S, Petit I, Porozov S, et al. CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Res 2004; 64:2817-2824.
31. Rombouts EJ, Pavic B, Lowenberg B, Ploemacher RE. Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia. Blood 2004; 104:550-557.
32. Zeng Z, Samudio IJ, Munsell M, et al. Inhibition of CXCR4 with the novel RCP168 peptide overcomes stroma-mediated chemoresistance in chronic and acute leukemias. Mol Cancer Ther 2006; 5:3113-3121. This work, using the synthetic peptide SDF-1 antagonist RCP168, provides evidence that inhibition of the CXCR4/SDF-1 interaction of the leukemia cells and marrow stroma is a novel therapeutic strategy for AML.
33. Jin L, Hope KJ, Zhai Q, et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 2006; 12:1167-1174. This report elegantly demonstrates that disruption of homing of LSCs to their supporting microenvironmental niche using an anti-CD44 monoclonal antibody can eradicate the LSC population.
34. Charrad RS, Li Y, Delpech B, et al. Ligation of the CD44 adhesion molecule reverses blockage of differentiation in human acute myeloid leukemia. Nat Med 1999; 5:669-676.
35. Legras S, Gunthert U, Stauder R, et al. A strong expression of CD44-6v correlates with shorter survival of patients with acute myeloid leukemia. Blood 1998; 91:3401-3413.
36. Krause DS, Lazarides K, von Andrian UH, Van Etten RA. Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nat Med 2006; 12:1175-1180. Genetic evidence that CD44 mediates the homing of BCR-ABL (breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1) expressing cells and that interaction of leukemia initiating cells with the bone marrow microenvironment is an essential step in leukemogenesis.
37. Ernst P, Wang J, Korsmeyer SJ. The role of MLL in hematopoiesis and leukemia. Curr Opin Hematol 2002; 9:282-287.
38. Scholl C, Bansal D, Dohner K, et al. The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis. J Clin Invest 2007; 117:1037-1048. This report provides evidence that disruption of the HOX genes pathways that occurs in the majority of cases of AML can be linked to aberrant expression of CDX2.
39. Rice KL, Licht JD. HOX deregulation in acute myeloid leukemia. J Clin Invest 2007; 117:865-868. This is a review of the role of CDX2 and HOX genes in hematopoiesis and AML.
40. Rawat VP, Cusan M, Deshpande A, et al. Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse model of t(12;13)(p13;q12) acute myeloid leukaemia. Proc Natl Acad Sci USA 2004; 101:817-822.
41. Rawat VP, Thoene S, Naidu VM, et al. Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia. Blood 2008; 111:309-319.
42. Milne TA, Briggs SD, Brock HW, et al. MLL targets SET domain methyl-transferase activity to Hox gene promoters. Mol Cell 2002; 10:1107-1117.
43. Okada Y, Feng Q, Lin Y, et al. hDOT1L links histone methylation to leukemogenesis. Cell 2005; 121:167-178.
44. Okada Y, Jiang Q, Lemieux M, et al. Leukaemic transformation by CALM-AF10 involves upregulation of Hoxa5 by hDOT1L. Nat Cell Biol 2006; 8:1017-1024. This report demonstrates that upregulation of HOX genes by the HMD hDOT1L is an underlying mechanism of leukemic transformation for CALM-AF10. The data demonstrate that recruitment of hDOT1L is not specific to MLL fusion proteins, and may be a common mechanism in AML pathogenesis.
45. Mueller D, Bach C, Zeisig D, et al. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 2007; 110:4445-4454.
46. Wang GG, Cai L, Pasillas MP, Kamps MP. NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Nat Cell Biol 2007; 9:804-812. Aberrant H3K36 methylation, a mark of transcriptional activation mediated by Nup98-NSD1, opposes the repressive effect of EZH2 (enhancer of zeste homolog 2) and leads to over-expression of HOX genes.
47. Kubicek S, O'Sullivan RJ, August EM, et al. Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 2007; 25:473-481. This group identified an inhibitor highly specific for its target G9a. This agent and others that target HMTs represent a possible new class of therapeutic agents.
48. Huang TS, Myklebust LM, Kjarland E, et al. LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis in vitro. Mol Cancer 2007; 6:31.
49. Raponi M, Harousseau JL, Lancet JE, et al. Identification of molecular predictors of response in a study of tipifarnib treatment in relapsed and refractory acute myelogenous leukemia. Clin Cancer Res 2007; 13:2254-2260.
50. Shibolet O, Giallourakis C, Rosenberg I, et al. AKAP13 a RhoA GTPase-specific guanine exchange factor is a novel regulator of TLR2 signaling. J Biol Chem 2007; 282:35308-35317.
51. Yin B, Tsai ML, Hasz DE, et al. A microarray study of altered gene expression after cytarabine resistance in acute myeloid leukemia. Leukemia 2007; 21:1093-1097.