Blood Res.  2014 Dec;49(4):241-245. 10.5045/br.2014.49.4.241.

Aberrant myeloid antigen co-expression is correlated with high percentages of CD34-positive cells among blasts of acute lymphoblastic leukemia patients: an Indian tertiary care center perspective

• Sharma RK
• Purohit A
• Somasundaram V
• Mishra PC
• Kotru M
• Ranjan R
• Kumar S
• Sazawal S
• Pati HP
• Tyagi S
• Saxena R

• KMID: 2270681
• DOI: http://doi.org/10.5045/br.2014.49.4.241

Abstract

BACKGROUND
Aberrant myeloid antigen (MA) co-expression and high expression of CD34 antigen on the blasts of acute lymphoblastic leukemia (ALL) patients are independently reported to have a role in pathogenesis and prognosis. This study was conducted to determine whether these two parameters are related.
METHODS
A total of 204 cases of ALL were included in an analysis of blast immunophenotypic data. CD34 expression was categorized as low when less than 50% of blasts were CD34-positive (CD34low) and as high when 50% or more were CD34-positive (CD34high).
RESULTS
Of 204 cases of ALL, 163 and 41 were of B-cell origin (B-ALL) and T-cell origin (T-ALL), respectively. Of all cases, 132 (64.7%) showed co-expression of MA and among these, 101 (76.51%) were CD34high, while the remaining 31 (23.48%) were CD34low. Of 72 cases without MA co-expression, 25 (34.72%) were CD34high and 47 (67.25%) were CD34low. Furthermore, of 163 cases of B-ALL, 111 showed co-expression of MA and 84 of these were CD34high. Of 52 cases of B-ALL without MA expression, 22 were CD34high. Among 41 cases of T-ALL, 21 co-expressed MA, 17 of which were CD34high. Moreover, all 20 cases of T-ALL without co-expression of MA were CD34low. These differences were statistically significant.
CONCLUSION
We observed a strong correlation between aberrant MA expression and CD34high expression on the blasts of ALL. We hypothesize that these different patient subsets may represent unique prognostic characteristics.

Keyword

CD34; Acute lymphoblastic leukemia; Immunophenotyping; Aberrant myeloid antigen co-expression; Flow cytometry

MeSH Terms

Antigens, CD34
B-Lymphocytes
Flow Cytometry
Humans
Immunophenotyping
Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
T-Lymphocytes
Tertiary Care Centers*
Antigens, CD34

Figure

• 

  Fig. 1 Flow cytometric dot plots representing variable CD34 positivity in blasts of acute lymphoblastic leukemia. Dot plot (A) is representative of CD34low and dot plot (B) is representative of CD34high.

• 

  Fig. 2 Frequencies of different patient subsets with respect to their association of myeloid antigen co-expression and CD34 percentage.

Reference

1. Tijchon E, Havinga J, van Leeuwen FN, Scheijen B. B-lineage transcription factors and cooperating gene lesions required for leukemia development. Leukemia. 2013; 27:541–552. PMID: 23047478.

2. Drexler HG, Thiel E, Ludwig WD. Review of the incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia. Leukemia. 1991; 5:637–645. PMID: 1886419.

3. Shen HQ, Tang YM, Yang SL, et al. Immunophenotyping of 222 children with acute leukemia by multi-color flow cytometry. Zhonghua Er Ke Za Zhi. 2003; 41:334–337. PMID: 14751050.

4. Vitale A, Guarini A, Ariola C, et al. Absence of prognostic impact of CD13 and/or CD33 antigen expression in adult acute lymphoblastic leukemia. Results of the GIMEMA ALL 0496 trial. Haematologica. 2007; 92:342–348. PMID: 17339183.

5. Sobol RE, Mick R, Royston I, et al. Clinical importance of myeloid antigen expression in adult acute lymphoblastic leukemia. N Engl J Med. 1987; 316:1111–1117. PMID: 3494942.

6. Uckun FM, Sather HN, Gaynon PS, et al. Clinical features and treatment outcome of children with myeloid antigen positive acute lymphoblastic leukemia: a report from the Children's Cancer Group. Blood. 1997; 90:28–35. PMID: 9207434.

7. Katz FE, Tindle R, Sutherland DR, Greaves MF. Identification of a membrane glycoprotein associated with haemopoietic progenitor cells. Leuk Res. 1985; 9:191–198. PMID: 3857408.

8. van Stijn A, van der Pol MA, Kok A, et al. Differences between the CD34+ and CD34- blast compartments in apoptosis resistance in acute myeloid leukemia. Haematologica. 2003; 88:497–508. PMID: 12745269.

9. Oyan AM, Bo TH, Jonassen I, et al. CD34 expression in native human acute myelogenous leukemia blasts: differences in CD34 membrane molecule expression are associated with different gene expression profiles. Cytometry B Clin Cytom. 2005; 64:18–27. PMID: 15668952.

10. Borowitz MJ, Shuster JJ, Civin CI, et al. Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a Pediatric Oncology Group study. J Clin Oncol. 1990; 8:1389–1398. PMID: 1696310.

11. Terstappen LW, Safford M, Konemann S, et al. Flow cytometric characterization of acute myeloid leukemia. Part II. Phenotypic heterogeneity at diagnosis. Leukemia. 1992; 6:70–80. PMID: 1540262.

12. Jennings CD, Foon KA. Recent advances in flow cytometry: application to the diagnosis of hematologic malignancy. Blood. 1997; 90:2863–2892. PMID: 9376567.

13. Pui CH, Behm FG, Crist WM. Clinical and biologic relevance of immunologic marker studies in childhood acute lymphoblastic leukemia. Blood. 1993; 82:343–362. PMID: 8329694.

14. Pui CH, Raimondi SC, Hancock ML, et al. Immunologic, cytogenetic, and clinical characterization of childhood acute lymphoblastic leukemia with the t(1;19) (q23; p13) or its derivative. J Clin Oncol. 1994; 12:2601–2606. PMID: 7989935.

15. Borkhardt A, Cazzaniga G, Viehmann S, et al. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Munster Study Group. Incidence and clinical relevance of TEL/AML1 fusion genes in children with acute lymphoblastic leukemia enrolled in the German and Italian multicenter therapy trials. Blood. 1997; 90:571–577. PMID: 9226156.

16. De Zen L, Orfao A, Cazzaniga G, et al. Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia: correlation with specific genotype. I. ETV6/AML1 ALLs identification. Leukemia. 2000; 14:1225–1231. PMID: 10914546.

17. Pui CH, Frankel LS, Carroll AJ, et al. Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases. Blood. 1991; 77:440–447. PMID: 1991161.

18. Pui CH, Hancock ML, Head DR, et al. Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia. Blood. 1993; 82:889–894. PMID: 7687897.

19. Vanhaeke DR, Bene MC, Garand R, Faure GC. Expression and long-term prognostic value of CD34 in childhood and adult acute lymphoblastic leukemia. Leuk Lymphoma. 1995; 20:137–142. PMID: 8750635.

20. Thomas X, Archimbaud E, Charrin C, Magaud JP, Fiere D. CD34 expression is associated with major adverse prognostic factors in adult acute lymphoblastic leukemia. Leukemia. 1995; 9:249–253. PMID: 7532767.

21. Craddock KJ, Chen Y, Brandwein JM, Chang H. CD13 expression is an independent adverse prognostic factor in adults with Philadelphia chromosome negative B cell acute lymphoblastic leukemia. Leuk Res. 2013; 37:759–764. PMID: 23643324.