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Negative prognostic value of CD34 antigen also if expressed on a small population of acute promyelocitic leukemia cells

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Abstract

Potential clinical significance of CD34 expression in acute promyelocitic leukemia (APL) has not been deeply investigated. We hereby analyzed the clinico-biological features and treatment outcome of APL patients in relation to CD34 expression, even when expressed in a small subpopulation: 114 APL patients homogeneously treated with the AIDA schedule were included in the study and prognostic correlation with respect to CD34 expression, both when expressed in association with CD2 and as isolated expression (cutoff ≥2 to <10 % or ≥10 %), were investigated. CD34 was associated to CD2 in 30 patients and was isolated in 19 patients. When compared to the CD34-negative population, CD34/CD2 expression identified a subgroup with characteristic features: M3 variant subtype (26 vs 7 % in the negative group, p = 0.02), bcr3 transcript subtype (73 vs 32 %, p = 0.001), high risk according to the risk of relapse (66 vs 17 %, p = 0.002), high incidence of differentiation syndrome (26 vs 12 %, p = 0.01), lower overall survival (88 vs 95 %), and a significantly higher rate of relapse (22 vs 13.8 %, p = 0.05). We then evaluated the prognostic value of isolated CD34 expression: it was detected in nine patients with a cutoff of expression ≥10 % and in 10 patients with a cutoff ≥2 but <10 %. Isolated CD34 positivity identified a subgroup with a classic morphology (79 %), bcr1 prevalence (53 %), higher rate of relapse (37 vs 13.8 % in the negative group, p = 0.002), higher incidence of differentiation syndrome (55 vs 12 %, p = 0.03), and lower overall survival (60 vs 95 %, p = 0.001). The results of our study confirm that CD34/CD2 expression characterizes a subset of APL with a high WBC count and a variant morphological subtype, associated with an unfavorable clinical course. We also show that the isolated expression of CD34, even at a low cutoff, identifies a group of classic APL with a negative prognosis. Further studies aimed at identifying other molecular signatures in CD34-positive patients are needed in order to optimize the therapeutic strategy for this subset of patients.

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References

  1. Sanz MA, Jarque I, Martin G (1988) Acute promyelocytic leukaemia therapy: results and prognostic factors. Cancer 1:7–13

    Article  Google Scholar 

  2. Tallman MS, Kwaan HC (1992) Reassessing the hemostatic disorder associated with acute promyelocytic leukaemia. Blood 79:543–53

    PubMed  CAS  Google Scholar 

  3. Dombret H, Scrobohaci ML, Ghorra P, Zini JM, Daniel MT, Castaigne S, Degos L (1993) Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. Leukemia 7:2–9

    PubMed  CAS  Google Scholar 

  4. Tallman MS, Lefebvre P, Baine RM, Shoji M, Cohen I, Green D et al (2004) Effects of all-trans retinoic acid or chemotherapy on the molecular regulation of systemic blood coagulation and fibrinolysis in patients with acute promyelocytic leukaemia. J Thromb Haemostasis 2:1341–1350

    Article  CAS  Google Scholar 

  5. Sanz MA, Lo Coco F (2011) Modern approaches to treating acute promyelocytic leukemia. J Clin Oncol 29:495–503

    Article  PubMed  Google Scholar 

  6. Paietta E (2003) Expression of cell-surface antigens in acute promyelocytic leukaemia. Best Pract Res Clin Haematol 16:369–385

    Article  PubMed  CAS  Google Scholar 

  7. Guglielmi C, Martelli MP, Diverio D, Fenu S, Vegna ML, Cantù-Rajnoldi A et al (1998) Immunophenotype of adult and childhood acute promyelocytic leukaemia: correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases. Br J Haematol 102:1035–1041

    Article  PubMed  CAS  Google Scholar 

  8. Foley R, Soamboonsrup P, Carter RF, Benger A, Meyer R, Walker I et al (2001) CD34-positive acute promyelocytic leukaemia is associated to leukocytosis, microgranular/hypogranular morphology, expression of CD2 and bcr3 isoform. Am J Hematol 67:34–41

    Article  PubMed  CAS  Google Scholar 

  9. Albano F, Mestice A, Pannunzio A, Lanza F, Martino B, Pastore D et al (2006) The biological characteristics of CD34 + CD2+ adult acute promyelocytic leukemia and the CD34-CD2- hypergranular and microgranular phenotypes. Haematologica 91:311–316

    PubMed  CAS  Google Scholar 

  10. Avvisati G, Lo Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M et al (2011) AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood 117:4716–4725

    Article  PubMed  CAS  Google Scholar 

  11. Lo Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A et al (2010) Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA 2000 trial of the GIMEMA group. Blood 116:3171–3179

    Article  PubMed  CAS  Google Scholar 

  12. Diverio D, Riccioni R, Pistilli A, Buffolino S, Avvisati G, Mandelli F, Lo Coco F (1996) Improved rapid detection of the PML/RARalpha fusion gene in acute promyelocytic leukemia. Leukemia 10:1214–1216

    PubMed  CAS  Google Scholar 

  13. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Annal Biochem 162:156–159

    Article  CAS  Google Scholar 

  14. van Dongen JJ, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G et al (1999) Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia 13:1901–1928

    Article  PubMed  Google Scholar 

  15. Noguera NI, Breccia M, Divona M, Diverio D, Costa V, De Santis S et al (2002) Alterations of the FLT3 gene in acute promyelocytic leukemia: association with diagnostic characteristics and analysis of clinical outcome in patients treated with the Italian AIDA protocol. Leukemia 16:2185–2189

    Article  PubMed  CAS  Google Scholar 

  16. Sanz MA, Lo Coco F, Martin G, Avvisati G, Rayon C, Barbui T et al (2000) Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood 96:1247–53

    PubMed  CAS  Google Scholar 

  17. Frankel SR (1992) (1992). The “retinoic acid syndrome” in acute promyelocytic leukemia. Ann Intern Med 117:292–296

    Article  PubMed  CAS  Google Scholar 

  18. Paietta E, Goloubeva O, Neuberg D, Bennett JM, Gallagher R, Racevskis J et al (2004) A surrogate marker profile for PML/RAR alpha expressing acute promyelocytic leukemia and the association of immunophenotypic markers with morphologic and molecular subtypes. Cytometry B Clin Cytom 59:1–9

    Article  PubMed  CAS  Google Scholar 

  19. Grimwade D, Outram SV, Flora R, Ings SJ, Pizzey AR, Morilla R et al (2002) The T-lineage affiliated CD2 gene lies within an open chromatin environment in acute promyelocytic leukaemia cells. Cancer Res 62:4730–4735

    PubMed  CAS  Google Scholar 

  20. Claxton DF, Reading CL, Nagarajan L, Tsujimoto Y, Andersson BS, Estey E et al (1992) Correlation of CD2 expression with PML gene breakpoints in patients with acute promyelocytic leukaemia. Blood 80:582–586

    PubMed  CAS  Google Scholar 

  21. Lin P, Hao S, Medeiros LJ, Estey EH, Pierce SA, Wang X et al (2004) Expression of CD2 in acute promyelocytic leukaemia correlates with short form of PML-RARa transcripts and poorer prognosis. Am J Clin Pathol 121:402–407

    Article  PubMed  CAS  Google Scholar 

  22. Gilliland DG, Griffin JD (2002) The roles of FLT3 in hematopoiesis and leukaemia. Blood 100:132–1542

    Article  Google Scholar 

  23. Chillon MC, Santamaria C, Garcia-Sanz R, Balanzategui A, Sarasquete ME, Alcoceba M et al (2010) Long FLT3 internal tandem duplications and reduced PML-RARα expression at diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia patients. Haematologica 95:745–751

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Schnittger S, Bacher U, Haferlach C, Kern W, Alpermann T, Haferlach T (2011) Clinical impact of FLT3 mutation load in acute promyelocytic leukemia with t(15;17)/PML-RARA. Haematologica 96:1799–1807

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Gale RE, Hills R, Pizzey AR, Kottaridis PD, Swirsky D, Gilkes AF, Adult Leukemia Working Party NCRI et al (2005) Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia. Blood 106:3768–3776

    Article  PubMed  CAS  Google Scholar 

  26. Marasca R, Maffei R, Zucchini P, Castelli I, Saviola A, Martinelli S et al (2006) Gene expression profiling of acute promyelocytic leukaemia identifies two subtypes mainly associated with FLT3 mutational status. Leukemia 20:103–114

    Article  PubMed  CAS  Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest. Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Department of Cellular Biotechnologies and Hematology, Sapienza University, Via Benevento 6, 00161, Rome, Italy

    Massimo Breccia, Maria Stefania De Propris, Caterina Stefanizzi, Sara Raponi, Matteo Molica, Gioia Colafigli, Clara Minotti, Roberto Latagliata, Daniela Diverio, Anna Guarini & Robin Foà

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  1. Massimo Breccia
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  2. Maria Stefania De Propris
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  3. Caterina Stefanizzi
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  4. Sara Raponi
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  6. Gioia Colafigli
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  7. Clara Minotti
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  11. Robin Foà
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Correspondence to Massimo Breccia.

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Breccia, M., De Propris, M.S., Stefanizzi, C. et al. Negative prognostic value of CD34 antigen also if expressed on a small population of acute promyelocitic leukemia cells. Ann Hematol 93, 1819–1823 (2014). https://doi.org/10.1007/s00277-014-2130-0

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  • DOI: https://doi.org/10.1007/s00277-014-2130-0

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