Acute Myeloid Leukemia
Diagnosis
Prognostically useful gene-expression profiles in acute myeloid leukemia.
Valk PJ, Verhaak RG, Beijen MA, et al.
N Engl J Med. 2004;350:1617-1628.
Description: Results of gene-expression profiling in 285 patients with AML to identify prognostically important clusters.
PubMed citation number: 15084694
Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics.
Marcucci G, Mrozek K, Bloomfield CD.
Curr Opin Hematol. 2005;12:68-75.
Description: Review of recent literature addressing the use of prognostic biomarkers (the internal tandem duplication and point mutations in the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA gene, and overexpression of the BAALC gene) in patients with AML and a normal karyotype. PubMed citation number: 15604894
Cytogenetics in acute leukemia.
Mrozek K, Heerema NA, Bloomfield CD.
Blood Rev. 2004;18:115-136.
Description: Review of the prognostic significance of all major cytogenetic abnormalities in adult AML or ALL with several useful tables.
PubMed citation number: 15010150
Cytogenetic pattern in acute myelogenous leukemia: a major reproducible determinant of outcome.
Keating MJ, Smith TL, Kantarjian H, et al.
Leukemia. 1988;2:403-412.
Description: The first study to show that cytogenetic profile is an independent predictor of response to treatment and duration of remission in AML.
PubMed citation number: 3164797
Pathophysiology
Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML.
Kakizuka A, Miller WH Jr, Umesono K, et al.
Cell. 1991;66:663-674.
Description: This study identified PML-RARa as the product of the t(15;17) translocation in acute promyelocytic leukemia and suggested that nonliganded PML-RARa functions as a novel dominant-negative oncogene that arrests myelocytic differentiation.
PubMed citation number: 1652368
Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy: a Southwest Oncology Group study.
Leith CP, Kopecky KJ, Godwin J, et al.
Blood. 1997;89:3323-3329.
Description: This study revealed that elderly patients with AML frequently overexpress the multidrug resistance protein MDR1, and that this is an independent prognostic marker for resistant disease.
PubMed citation number: 9129038
Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis.
Thiede C, Steudel C, Mohr B, et al.
Blood. 2002;99:4326-4335.
Description: One of several studies demonstrating a high incidence of FLT3 receptor tyrosine kinase–activating mutations in acute myeloid leukemia (internal tandem duplication of the juxtamembrane region in 20.4% of cases or point mutations in the second tyrosine kinase domain in 7.7% of cases). This study also demonstrated that a high ratio of mutant to wild-type FLT3 is an independent prognostic marker for disease-free and overall survival.
PubMed citation number: 12036858
Internal tandem duplications of the FLT3 gene are present in leukemia stem cells.
Levis M, Murphy KM, Pham R, et al.
Blood. 2005;106:673-680.
Description: Study demonstrating the presence of internal tandem duplication mutations of the FLT3 gene in leukemic stem cells, and that FLT3 inhibitors may have therapeutic activity.
PubMed citation number: 15797998
C-kit as a target in the treatment of acute myelogenous leukemia.
Advani AS.
Curr Hematol Rep. 2005;4:51-58.
Description: Discussion of the biology of c-kit (which is present on >10% of blasts in 64% of de novo and 95% of relapsed AMLs) and a review of the results of trials targeting c-kit in AML.
PubMed citation number: 15610660
Treatment
Treatment of acute myelocytic leukemia: a study by cancer and leukemia group B.
Rai KR, Holland JF, Glidewell OJ, et al.
Blood. 1981;58:1203-1212.
Description: The prospective, randomized trial that demonstrated the superiority of the “7 and 3” regimen of cytarabine and daunorubicin as induction therapy for AML.
PubMed citation number: 6946847
Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission.
Cassileth PA, Harrington DP, Appelbaum FR, et al.
N Engl J Med. 1998;339:1649-1656.
Description: This study failed to show an advantage of autologous or allogeneic bone marrow transplantation compared with chemotherapy (high-dose cytarabine consolidation) for patients with acute myeloid leukemia in first complete remission after induction therapy (and in fact suggested an overall survival advantage for patients treated with chemotherapy).
PubMed citation number: 9834301
Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse.
Sievers EL, Larson RA, Stadtmauer EA, et al; Mylotarg Study Group.
J Clin Oncol. 2001;19:3244-3254.
Description: This study established the effectiveness of an antibody-targeted chemotherapy agent in patients with relapsed CD33 + acute myeloid leukemia, providing impetus for the use of monoclonal antibodies as a way of targeting leukemic cells.
PubMed citation number: 11432892
Recent advances in the development of small-molecule inhibitors for the treatment of acute myeloid leukemia.
Levis M.
Curr Opin Hematol. 2005;12:55-61.
Description: Review of recent advances in the development of small-molecule inhibitors of molecular signaling pathways for the treatment of AML.
PubMed citation number: 15604892
Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia.
Huang ME, Ye YC, Chen SR, et al.
Blood. 1988;72:567-572.
Description: This was the first report in the English literature describing the effectiveness of all-trans retinoic acid for the treatment of acute promyelocytic leukemia.
PubMed citation: 3165295
A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia: the European APL Group.
Fenaux P, Chastang C, Chevret S, et al.
Blood. 1999;94:1192-1200.
Description: This study demonstrated that the use of chemotherapy with ATRA during induction therapy and the subsequent use of low-dose chemotherapy with intermittent ATRA for maintenance improve relapse-free survival.
PubMed citation number: 10438706
Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL), II: clinical efficacy and pharmacokinetics in relapsed patients.
Shen ZX, Chen GQ, Ni JH, et al.
Blood. 1997;89:3354-3360.
Description: This was the first study published in the English literature demonstrating the activity of arsenic trioxide in patients with relapsed acute promyelocytic leukemia (9 out of 10 patients achieving complete remission).
PubMed citation number: 9129042
Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia.
Sanz MA, Tallman MS, Lo-Coco F.
Blood. 2005;105:3019-3025.
Description: Review of treatment in APL with special attention to appropriate diagnosis, supportive care, management of its unique complications, and special issues in elderly or pregnant patients.
PubMed citation number: 15604216
Review
Possibilities for tailored and targeted therapy in paediatric acute myeloid leukemia.
Zwaan CM, Kaspers GJ.
Br J Haematol. 2004;127:264-279.
Description: Review of prognosis, outcomes, recent clinical trials, genetic mutations, drug resistance, and standard and emerging therapies in pediatric AML.
PubMed citation number: 15491285
Bone marrow transplantation for paediatric AML in first remission: a systematic review and meta-analysis.
Bleakley M, Lau L, Shaw PJ, Kaufman A.
Bone Marrow Transplant. 2002;29:843-852.
Description: Systematic review and meta-analysis of trials from 1985-2000 to evaluate the effectiveness of stem cell transplantation or intensive chemotherapy in children with AML in first remission.
PubMed citation number: 12058234
Management of acute myeloid leukemia in elderly patients.
Hiddemann W, Kern W, Schoch C, et al.
J Clin Oncol. 1999;17:3569-3576.
Description: Review of clinical trials guiding the optimal management of AML in the elderly.
PubMed citation number: 10550156
Acute myeloid leukemia.
Stone RM, O'Donnell MR, Sekeres MA.
Hematology (Am Soc Hematol Educ Program). 2004:98-117.
Description: Review which includes discussion of the optimal management of AML (induction and postremission therapy, auto- or allogeneic stem cell transplantation, and emerging agents such as FLT-3 or farnesyl transferase inhibitors) in adults and elderly patients.
PubMed citation number: 15561679
Adult acute myeloid leukaemia.
Smith M, Barnett M, Bassan R, Gatta G, Tondini C, Kern W.
Crit Rev Oncol Hematol. 2004;50:197-222.
Description: Review of the incremental improvements in survival for AML in various patient subsets with focus on prognostic classification, conventional therapy, auto- and allogeneic stem cell transplantation, and emerging therapeutics.
PubMed citation number: 15182826
Unanswered questions in acute myeloid leukaemia.
Ferrara F.
Lancet Oncol. 2004;5:443-450.
Description: Expert opinion of the appropriate treatment for AML in various patient populations based on the past 20 years worth of evidence and clinical trials, with consideration of unanswered questions and controversies.
PubMed citation number: 15231251