DOI QR코드

DOI QR Code

Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia: A Retrospective Cohort Study in Makah Al Mukaramah, Saudi Arabia

  • 발행 : 2014.01.15

초록

Background: Aberrant phenotypes in acute leukemia have variable frequency and their prognostic and predictive relevance is controversial, despite several reports of clinical significance. Aims: To determine the prevalence of aberrant antigen expression in acute leukemia, assess clinical relevance and demonstrate immunophenotype-karyotype correlations. Materials and Methods: A total of 73 (40 AML and 33 ALL) newly diagnosed acute leukemia cases presenting to KAMC, Kingdom of Saudi Arabia, were included. Diagnosis was based on WHO criteria and FAB classification. Immunophenotyping by flow cytometry, conventional karyotyping and fluorescence in situ hybridization for gene rearrangements were performed. Results: Aberrant antigens were detected in 27/40 (67.5%) of AML and in 14/33 (42.4%) in ALL cases. There were statistically significant higher TLC in Ly+ AML than in Ly-AML (p=0.05) and significant higher blast count in ALL with aberrant antigens at presentation and day 14 (p=0.005, 0.046). There was no significant relation to clinical response, relapse free survival (RFS) or overall survival (p>0.05), but AML cases expressing ${\geq}2$ Ly antigens showed a lower median RFS than those expressing a single Ly antigen. In AML, CD 56 was expressed in 11/40. CD7 was expressed in 7/40, having a significant relation with an unfavorable cytogenetic pattern (p=0.046). CD4 was expressed in 5/40. CD19 was detected in 4/40 AML associated with M2 and t (8; 21). In ALL cases, CD33 was expressed in 7/33 and CD13 in 5/33. Regarding T Ag in B-ALL CD2 was expressed in 2 cases and CD56 in 3 cases. Conclusions: Aberrant antigen expression may be associated with adverse clinical data at presentation. AML cases expressing ${\geq}2$ Ly antigens may have shorter median RFS. No specific cytogenetic pattern is associated with aberrant antigen expression but individual antigens may be related to particular cytogenetic patterns. Immunophenotype-karyotype correlations need larger studies for confirmation.

키워드

참고문헌

  1. Ahmed D, Ahmed T, Ahmed S, Tipu H, Wiqar M (2008). CD5-positive acute lymphoblastic leukemia. J Coll Physicians Surg Pak, 18, 310-1.
  2. Al-Mawali A, Gillis D, Hissaria P, Lewis I (2008). Incidence, sensitivity, and specificity of leukemia-associated phenotypes in acute myeloid leukemia using specific five-color multiparameter flow cytometry. Am J Clinical Pathol, 129, 934-45. https://doi.org/10.1309/FY0UMAMM91VPMR2W
  3. Anjali S, Gundacker H, Marilyn L, et al (2011). Outcome and Prevalence of Hyperdiploidy and Hypodiploidy in Adults with Newly Diagnosed Acute Lymphocytic Leukemia: A SWOG Study. Poster in 53th ASH annual meeting and exposition 2011, http://oncology.by/uplds/ASH/MAC/webprogramcd/Paper38358.html (2013-04-07)
  4. Bagg A (2007). Lineage ambiguity, infidelity, and promiscuity in immunophenotypically complex acute leukemias: genetic and morphologic correlates. Am J Pathol, 128, 545-8.
  5. Bahia D, Yamamoto M, Chauffaille M, et al (2001). Aberrant phenotypes in acute myeloid leukemia: a high frequency and clinical significance. haematologica, 86, 801-6.
  6. Behm F, Raimondi S, Schell M, et al (1992). Lack of CD45 antigen on blast cells in childhood acute lymphoblastic leukemia is associated with chromosomal hyperdiploidy and other favorable prognostic features. Blood, 79, 1011-6.
  7. Bhushan B, Chauhan P, Saluja S, et al (2010). Aberrant phenotypes in childhood and adult acute leukemia and its association with adverse prognostic factors and clinical outcome. Clin Exp Med, 10, 33-40. https://doi.org/10.1007/s10238-009-0067-8
  8. Buccisano F, Maurillo L, Spagnoli A, et al (2009). Monitoring of minimal residual disease in acute myeloid leukemia. Current Opinion in Oncol, 21, 582-8. https://doi.org/10.1097/CCO.0b013e3283311856
  9. Chang H, Yeung J, Brandwein J, Yi Q (2007). CD7 expression predicts poor disease free survival and post-remission survival in patients with acute myeloid leukemia and normal karyotype. Leukemia Res, 31, 157-62. https://doi.org/10.1016/j.leukres.2006.06.001
  10. Cruse J, Lewis R, Pierce S, Lam J, Tadros Y( 2005). Aberrant expression of CD7, CD56, CD79a antigens in acute myeloid leukemia. Exp Mol Pathol, 79, 39-41. https://doi.org/10.1016/j.yexmp.2005.02.003
  11. Dunphy C (1999). Comprehensive review of adult acute myelogenous leukemia: cytomorphological, enzyme cytochemical, flow cytometric immunophenotypic, and cytogenetic findings. J Clin Laboratory Analysis, 13, 19-26. https://doi.org/10.1002/(SICI)1098-2825(1999)13:1<19::AID-JCLA4>3.0.CO;2-1
  12. El-Sissy A, El-Mashari M, Bassuni W, El-Swaayed A (2006). Aberrant Lymphoid Antigen Expression in Acute Myeloid Leukemia in Saudi Arabia. J Egypt Natl Canc Inst, 18, 244-9.
  13. Graf M, Reif S, Hecht K, et al (2005). High expression of co stimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML). Ann Hematol, 84, 287-97. https://doi.org/10.1007/s00277-004-0978-0
  14. Hur M, Chang Y, Lee D, Park M, Cho H (2001). Immunophenotypic and cytogenetic changes in acute leukaemia at relapse. Clin Lab Haematol, 23, 173-9. https://doi.org/10.1046/j.1365-2257.2001.00389.x
  15. Hurwitz C, Raimondi S, Head D, et al (1992). Distinctive immunophenotypic features of t (8; 21) (q22; q22) acute myeloblastic leukemia in children. Blood, 80, 3182-8.
  16. Hussein S, Gill K, Sireci A, et al (2011). Aberrant T-cell antigen expression in B lymphoblastic leukaemia. Br J Haematol, 155, 449-56. https://doi.org/10.1111/j.1365-2141.2011.08870.x
  17. ISCN (1985). An international system of human cytogenetic nomenclature: Birth Defects Origi Artic Ser, 21, 1-117.
  18. Jiang N, Chen X, Zhu H, et al (2010). Immunophenotype characteristics and prognosis of acute leukemia patients with cross expressing lymphoid and myeloid lineage associated antigens (abstract), Zhongguo Shi Yan Xue Ye Xue Za Zhi, 18, 1405-9.
  19. Kern W, Haferlach C, Haferlach T, Schnittger S(2008). Monitoring of minimal residual disease in acute myeloid leukemia. Cancer, 112, 4-16. https://doi.org/10.1002/cncr.23128
  20. Khoury H, Dalal B, Nevill T, et al (2003). Acute myelogenous leukemia with t (8; 21): identification of a specific immunophenotype. Leukaemia Lymphoma, 44, 1713-8. https://doi.org/10.1080/1042819031000116698
  21. Krasinskas A, Wasik M, Kamoun M, et al (1998). The usefulness of CD64, other monocyte-associated antigens, and CD45 gating in the sub classification of acute myeloid leukemia with monocytic differentiation. Am J Clinical Pathol, 110, 797-805.
  22. Lin P, Hao S, Medeiros L, et al (2004). Expression of CD2 in acute promyelocytic leukemia correlates with short form of PML-RARA alpha transcripts and poorer prognosis. Am J Clin Pathol, 121, 402-7. https://doi.org/10.1309/XC8P9M8NKQDT38LB
  23. Liu Y, Wang Y, Chen S, et al (2007). Analysis of immunophenotype and leukemia associated immunophenotype in 610 patients with acute myeloid leukemia. Zhonghua Xue Ye Xue Za Zhi, 28, 731-6 (in Chinese).
  24. Ludwig W, Rieder H, Bartram C, et al (1998). Immunophenotypic and genotypic features, clinical characteristics, and treatment outcome of adult pro-B acute lymphoblastic leukemia: results of the German multicenter trials GMALL 03/87 and 04/89. Blood, 92, 1898-909.
  25. Macedo A, Orfao A, Vidriales M, et al (1995). Characterization of aberrant phenotypes in acute myeloblastic leukemia. Ann Hematol, 70, 189-94. https://doi.org/10.1007/BF01700374
  26. Medeiros B, Kohrt H, Arber D, et al (2010). Immunophenotypic features of acute myeloid leukemia with inv (3) (q21q26.2)/ t(3; 3) (q21;q26.2). Leukemia Res, 34, 594-7. https://doi.org/10.1016/j.leukres.2009.08.029
  27. Novoa V, Nunez N, Carballo O, Lessa C (2013). Aberrant immunophenotypes in acute leukemia in a Buenos Aires' hospital population (abstract). Medicina, 73, 9-16
  28. Ogata K, Yokose N, Shioi Y, et al (2001). Reappraisal of the clinical significance of CD7 expression in association with cytogenetics in de novo acute myeloid leukemia. Br J Haematol, 115, 612-5 https://doi.org/10.1046/j.1365-2141.2001.03139.x
  29. Ossenkoppele G, Van de Loosdrecht A, Schuurhuis G (2011). Review of the relevance of aberrant antigen expression by flowcytometry in myeloid neoplasms. Br J Haematol, 153, 421-36. https://doi.org/10.1111/j.1365-2141.2011.08595.x
  30. Paietta E, Neuberg D, Richards S, et al (2001). Rare adult acute lymphocytic leukemia with CD56 expression in the ECOG experience shows unexpected phenotypic and genotypic heterogeneity. Am J Hematol, 66, 189-96. https://doi.org/10.1002/1096-8652(200103)66:3<189::AID-AJH1043>3.0.CO;2-A
  31. Peterson M, Noskoviak K, Newbury R (2007). CD5-positive B-cell acute lymphoblastic leukemia. Pediatr Dev Pathol, 10, 41-5. https://doi.org/10.2350/06-03-0057.1
  32. Pui C, Rubnitz J, Hancock M, et al (1998). Reappraisal of the clinical and biologic significance of myeloid-associated antigen expression in childhood acute lymphoblastic leukemia. J Clin Oncol, 16, 3768-73.
  33. Putti M, Rondelli R, Cocito M, et al (1998). Expression of myeloid markers lacks prognostic impact in children treated for acute lymphoblastic leukemia: Italian experience in AIEOP-ALL 88-91 studies. Blood, 92, 795-801
  34. Saxena A, Sheridan D, Card R, et al (1998). Biologic and clinical significance of CD7 expression in acute myeloid leukemia. Am J Hematol, 58, 278-84. https://doi.org/10.1002/(SICI)1096-8652(199808)58:4<278::AID-AJH5>3.0.CO;2-N
  35. Seegmiller A, Kroft S, Karandikar N and McKenna R (2009). Characterization of Immunophenotypic Aberrancies in 200 Cases of B Acute Lymphoblastic Leukemia. Am J Clin Pathol, 132, 940-9. https://doi.org/10.1309/AJCP8G5RMTWUEMUU
  36. Shen H, Tang Y, Yang S, et al (2003). Immunophenotyping of 222 children with acute leukemia by multi-color flow cytometry (abstract). Zhonghua Er Ke Za Zhi, 41, 334-7.
  37. Suggs J, Cruse J, Lewis R (2007). Aberrant myeloid marker expression in precursor B-cell and T-cell leukemias. Exp Mol Pathol, 83, 471-3. https://doi.org/10.1016/j.yexmp.2007.08.012
  38. Vardiman J, Thiele J, Arber D, et al (2009). The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 937-51. https://doi.org/10.1182/blood-2009-03-209262
  39. Venditti A, Del Poeta G, Buccisano F, et al ( 1998). Prognostic relevance of the expression of TdT and CD7 in 335 cases of acute myeloid leukemia. Leukemia, 12, 1056-63. https://doi.org/10.1038/sj.leu.2401067
  40. Vitale A, Guarini A, Ariola C, et al (2007). Absence of prognostic impact of CD13 and/or CD33 antigen expression in adult acute lymphoblastic leukemia. Results of the GIMEMA ALL 0496 trial. Haematologica, 92, 342-8 https://doi.org/10.3324/haematol.10385
  41. Voskova D, Valekova L, Fedorova J, Hudecek J, Kubisz P (2003). Leukemic cells and aberrant phenotypes in acute leukemia patients: a flow cytometry analysis. Neoplasma, 50, 422-7.
  42. Wang H, Cheng Y, Wang H, et al (2009). CD19-positive acute myeloblastic leukemia with trisomy 21 as a sole acquired karyotypic abnormality (abstract). J Zhejiang Univ Sci B, 10, 833-8. https://doi.org/10.1631/jzus.B0820362
  43. Wang X, Zheng J, Gu J, et al (2005).Correlation of immunophenotype to cytogenetics and clinical features of adult acute myeloid leukemia (abstract). Ai Zheng, 24, 667-71.
  44. Wiersma S, Ortega J, Sobel E, Weinberg K (1991). Clinical importance of myeloid-antigen expression in acute lymphoblastic leukemia of childhood. N Engl J Med, 324, 800-8. https://doi.org/10.1056/NEJM199103213241204
  45. Wu W, Liang J, Zhu M, Xue Y, Chen Z (2007). MIC categorization of acute lymphoblastic leukemia with myeloid surface antigen expression (abstract). Zhonghua Xue Ye Xue Za Zhi, 28, 754-6.
  46. Xu B, Hu C, Miao X, et al (2003). Immunophenotyping of 106 adult patients with acute leukemia by flow cytometry (abstract). Di Yi Jun Yi Da Xue Xue Bao; 23,1043-6.
  47. Zhang Y, Tan L, Hu Q, et al (2012). Immunophenotyping and its clinical significance in childhood acute lymphoblastic leukemia (abstract) Zhongguo Dang Dai Er Ke Za Zh, 14, 188-91.
  48. Zhu H, Niu T, Meng W, Xu C, Lei S (2002). Immunophenotype of acute leukemia and its clinical significance (abstract). Hua Xi Yi Ke Da Xue Bao, 33, 118-20.

피인용 문헌

  1. Immunophenotypic aberrancies in acute lymphoblastic leukemia from 282 Iraqi patients vol.39, pp.6, 2017, https://doi.org/10.1111/ijlh.12716
  2. Flow Cytometric Diagnosis of Acute Leukemia and Aberrant Antigen: Sohag University Experience vol.08, pp.02, 2018, https://doi.org/10.4236/ojbd.2018.82005
  3. Clinically useful flow cytometry approach to identify immunophenotype in acute leukemia pp.1473-2300, 2019, https://doi.org/10.1177/0300060518819637