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Background: Acute myeloid leukemia (AML) accounts for 25%-35% of the acute leukemia in children. BAALC (Brain and Acute Leukemia, Cytoplasmic gene) is a recently identified gene on chromosome 8q22.3 that has prognostic significance in AML. The aim of this work was to study the impact of BAALC gene expression on prognosis of AML in Egyptian children. Patients and methods: This study was conducted on 40 patients of newly diagnosed AML who were subjected to the following: Full history taking, clinical examination, laboratory investigations including: complete blood count, LDH, bone marrow aspiration, cytochemistry and immunophenotyping, assessment of BAALC Gene by real time PCR in bone marrow aspirate mononuclear cells before the start of chemotherapy. Results: BAALC gene expression showed positive expression in 24 cases (60%) and negative expression in 16 cases (40%). Patients who showed positive BAALC gene expression included 10 patients achieved complete remission, 8 patients died and 6 relapsed patients, while patients who showed negative expression include 12 patients achieved complete remission, 1 relapsed patient and 3 patients died. There was significant association between BAALC gene expression and FAB classification of patients of AML patientsas positive BAALC expression is predominantly seen in FAB subtypes M1 and M2 compared with negative BAALC gene expression that was found more in M3 and M4 (8 cases with M1, 12 cases with M2, 1 case with M3 and 3 cases with M4 in positive BAALC expression versus 2 cases with M1, 3 cases with M2, 4 cases with M3 and 7 cases with M4 in BAALC gene negative expression group with significant difference regarding FAB subtypes). As regard age, sex, splenomegaly, lymphadenopathy, pallor, purpura, platelets count, WBCs count, and percentage of blast cells in BM, the present study showed no significant association with BAALC. Conclusion: BAALC expression is an important prognostic factor in AML patients and its incorporation into novel risk-adapted therapeutic strategies will improve the currently disappointing cure rate of this group of patients.
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2. Juliusson G, Lazarevic VL, Horstedt AS, Hagberg O, Höglund M; Swedish Acute Leukemia Registry Group. Acute myeloid leukemia in the real word: Why population- based registries are needed Blood. 2012 Apr 26; 119(17):3890-9. doi: 10.1182/blood-2011-12-379008. Epub 2012 Mar 1.
3. Mro zek K, Marcucci G, Paschka P, Whitman SP, Bloomfield CD. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: Are we ready for a prognostically prioritized molecular classification? Blood 2007; 109:431-448.
4. Tanner SM, Austin JL, Leone G, Rush LJ, Plass C, Heinonen K, Mrózek K, Sill H, Knuutila S, Kolitz JE, Archer KJ, Caligiuri MA, Bloomfield CD, de La Chapelle. BAALC, the human member of a novel mammalian neuroectoderm gene lineage, is implicated in hematopoiesis and acute leukemia. Proc Natl Acad Sci U S A. 2001 Nov 20; 98(24):13901-6. Epub 2001 Nov 13.
5. Ilenčíková D, Sykora J, Mikulaon Z Repiská V. Identification of molecular markers in children with acute myeloid leukemia. Clin Oncol 2012; 25(1):26-35.
6. Eisfeld AK, Marcucci G, Liyanarachchi S, Döhner K, Schwind S, Maharry K, Leffel B, Döhner H, Radmacher MD, Bloomfield CD, Tanner SM, de la Chapelle A. . Heritable polymorphism predisposes to high BAALC expression in acute myeloid leukemia. Proc Natl Acad Sci U S A. 2012 Apr 24; 109(17):6668-73. doi: 10.1073/pnas.1203756109. Epub 2012 Apr 9.
7. Baldus CD, Martus P, Burmeister T, Schwartz S, Gökbuget N, Bloomfield CD, Hoelzer D, Thiel E, Hofmann WK. Low ERG and BAALC expression identifies a new subgroup of adult acute T Lymphoblastic leukemia with a highly favorable outcome. J Clin Oncal 2007 Aug 20; 25(24):3739-45. Epub 2007 Jul 23.
8. Santamaría C, Chillón MC, García-Sanz R, Pérez C, Caballero MD, Mateos MV, Ramos F, de Coca AG, Alonso JM, Giraldo P, Bernal T, Queizán JA, Rodríguez JN, Puig N, Balanzategui A, Sarasquete ME, Alcoceba M, Díaz-Mediavilla J, San Miguel J, González M. BAALC is an important predictor of refractoriness to chemotherapy and poor survival in intermediate-risk acute myeloid leukemia. Ann Hematol. 2010 May; 89(5):453-8. doi: 10.1007/s00277-009-0864-x. Epub 2009 Nov 27.
9. Byrd JC, Mrózek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC, Pettenati MJ, Patil SR, Rao KW, Watson MS, Koduru PR, Moore JO, Stone RM, Mayer RJ, Feldman EJ, Davey FR, Schiffer CA, Larson RA, Bloomfield CD; Cancer and Leukemia Group B (CALGB 8461). Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: Results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002 Dec 15; 100(13):4325-36. Epub 2002 Aug 1.
10. Boyam A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968; 97:77-89
11. Seville M, West AB, Cull MG, McHenry CS. Fluorometric assay for DNA polymerases and reverse transcriptase.Biotechniques1996;21(4):664,666,668,670,672.
12. Baladus A., Thiede C, Soucek S. BAALC expression and FLT-3 internal tandem duplication mutations in acute myeloid leukemia patients with normal cytogenetic: Prognostic implications .J Clin Oncol 2006; 24:790-7.
13. Hann IM, Webb DK, Gibson BE, Harrison CJ. MRC trials in childhood acute myeloid leukaemia. Ann Hematol 83 (Suppl 1): S108-12, 2004.
14. Gibson BE, Webb DK, Howman AJ, De Graaf SS, Harrison CJ, Wheatley K; United Kingdom Childhood Leukaemia Working Group and the Dutch Childhood Oncology Group. Results of a randomized trial in children with Acute Myeloid Leukemia: medical research council AML12 trial. Br J Haematol. 2011 Nov; 155(3):366-76. doi: 10.1111/j.1365-2141.2011.08851.x. Epub 2011 Sep 9.
15. Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. 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. Blood. 1999 Aug 15; 94(4):1192-200.
16. Ishikawa Y, Kiyoi H, Naoe T . Prevalence and clinical characteristics of N-terminally truncated WT1 expression in acute myeloid leukemia. Leuk Res. 2011 May; 35(5):685-8. doi: 10.1016/j.leukres.2011.01.002. Epub 2011 Jan 21.
17. Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European Leukemia Net. Diagnosis and management of AML in adults: Recommendation from an international expert panel, on behalf of the European leukemia net .Blood 2010 Jan 21; 115(3):453-474. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30
18. Yahya RS, Sofan MA, Abdelmasseih HM, Saudy N, Sharaf-Eldein MA. Prognostic implication of BAALC gene expression in adult acute myeloid leukemia Clin Lab. 2013; 59(5-6):621-8.
19. Damiani D, Tiribelli M, Franzoni A, Michelutti A, Fabbro D, Cavallin M, Toffoletti E, Simeone E, Fanin R, Damante G. BAALC overexpression retains its negative prognostic role across all cytogenetic risk groups in acute myeloid leukemia patients. Am J Hematol. 2013 Oct; 88(10):848-52. doi: 10.1002/ajh.23516. Epub 2013 Jul 23.
20. El-Sharnouby JA, Sayed Ahmed LM, Taha AM, Okasha K. Prognostic Significance of CEBPA Mutations and BAALC Expression in Acute Myeloid Leukemia Patients with Normal Karyotype. Eur J Gen Med 2010; 7(1):17-28.
21. Baldus CD, Tanner SM, Ruppert AS, Whitman SP, Archer KJ, Marcucci G, Caligiuri MA, Carroll AJ, Vardiman JW, Powell BL, Allen SL, Moore JO, Larson RA, Kolitz JE, de la Chapelle A, Bloomfield CD. BAALC expression predicts clinical outcome of de novo acute myeloid leukemia patients with normal cytogenetic: A Cancer and Leukemia Group B study. Blood. 2003 Sep 1; 102(5):1613-8. Epub 2003 May 15.
22. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell.2006 Mar;9(3):189-98.
23. Bienz M, Ludwig M, Leibundgut EO, Mueller BU, Ratschiller D, Solenthaler M, Fey MF, Pabst T. Risk assessment in patients with acute myeloid leukemia and a normal karyotype. Clin Cancer Res 2005 Feb 15; 11(4):1416-24.
24. Nibourel O, Kosmider O, Cheok M, Boissel N, Renneville A, Philippe N, Dombret H, Dreyfus F, Quesnel B, Geffroy S, Quentin S, Roche-Lestienne C, Cayuela JM, Roumier C, Fenaux P, Vainchenker W, Bernard OA, Soulier J, Fontenay M, Preudhomme C. . Incidence and prognostic value of TET2 alterations in de novo acute myeloid leukemia achieving complete remission. Blood. 2010 Aug 19; 116(7):1132-5. doi: 10.1182/blood-2009-07-234484. Epub 2010 May 20.
25. S Weber, T Alpermann, F Dicker, S Jeromin, N Nadarajah, C Eder, A Fasan1, A Kohlmann, M Meggendorfer, C Haferlach, W Kern, T Haferlach and S Schnittger. BAALC expression: a suitable marker for prognostic risk stratification and detection of residual disease in cytogenetically normal acute myeloid leukemia. Blood Cancer Journal 2014 January 10; 4, e173; doi:10.1038/bcj.2013.7