Ann Lab Med.  2019 Jul;39(4):358-366. 10.3343/alm.2019.39.4.358.

The Incidence and Immunophenotypic and Genetic Features of JL1 Expressing Cells and the Therapeutic Potential of an Anti-JL1 Antibody in De Novo Pediatric Acute Leukemias

Affiliations
  • 1Department of Laboratory Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Korea.
  • 2Department of Laboratory Medicine, Inje University College of Medicine, Busan Baik Hospital, Busan, Korea.
  • 3Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea. cjpark@amc.seoul.kr
  • 4Department of Pediatrics, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Abstract

BACKGROUND
JL1 is a newly identified CD43 epitope that specifically recognizes leukemic cells. We analyzed the incidence of JL1 expression and compared the clinical, immunophenotypic, and genetic characteristics of de novo pediatric acute leukemia patients with respect to JL1 expression status to determine the therapeutic potential of an anti-JL1 antibody.
METHODS
Seventy-eight patients with pediatric acute leukemia (52 with ALL, 26 with AML) diagnosed between December 2014 and January 2016 were enrolled prospectively. Flow cytometry for JL1 expression was performed at diagnosis. Clinical, immunophenotypic, and genetic characteristics were compared with respect to JL1 expression status by the Student t-test/Mann-Whitney U test and chi-square test/Fisher's exact test.
RESULTS
The incidence of JL1 expression was 76.9% and 84.6% in ALL and AML patients, respectively. ALL patients with JL1 expression showed higher CD10 and cytoplasmic IgM expressions than those without JL1 expression (P=0.022 and 0.003, respectively) and were associated with TCF3-PBX1 and KMT2A-MLLT1 translocations. AML patients with JL1 expression showed higher CD13 and lower CD65 and CD15 expressions than those without JL1 expression (P=0.013, 0.007, and 0.024, respectively) and were associated with RUNX1-RUNX1T1, PML-RARA, and CBFB-MYH11 translocations. The JL1 expression incidence did not differ between ALL and AML, and the JL1 expression status did not affect prognosis.
CONCLUSIONS
Our findings support the potential therapeutic role of anti-JL1 monoclonal antibodies; JL1 expression was associated with specific immunophenotypes and genetic abnormalities. Future studies should examine the prognostic impact of JL1 expression in pediatric acute leukemias.

Keyword

Immunophenotypic; Genetic; JL1 expression; Pediatric acute leukemias; Prognosis

MeSH Terms

Antibodies, Monoclonal
Cytoplasm
Diagnosis
Flow Cytometry
Humans
Immunoglobulin M
Incidence*
Leukemia*
Prognosis
Prospective Studies
Antibodies, Monoclonal
Immunoglobulin M

Figure

  • Fig. 1 Schematic illustration of JL1 expression analysis by flow cytometry. The initial cutoff threshold of fluorescence intensity for positive expression of JL1 determined using isotypic controls was validated with an internal control (lymphocytes) (A). JL1 expression in myeloid immature cells, and B-ALL examples of JL1 expression and without JL1 expression in leukemic blasts are given in (B–D), respectively (5.8%, 90.8%, and 3.9%, respectively).Abbreviations: CD, cluster of differentiations; SSC, side scattering; FSC, forward scattering; PE, phycoerythrin; APC, allophycocyanin.


Reference

1. Adams GP, Weiner LM. Monoclonal antibody therapy of cancer. Nat Biotechnol. 2005; 23:1147–1157. PMID: 16151408.
2. Gasparini G, Longo R, Torino F, Gattuso D, Morabito A, Toffoli G. Is tailored therapy feasible in oncology? Crit Rev Oncol Hematol. 2006; 57:79–101. PMID: 16337806.
3. Reichert JM, Rosensweig CJ, Faden LB, Dewitz MC. Monoclonal antibody successes in the clinic. Nat Biotechnol. 2005; 23:1073–1078. PMID: 16151394.
4. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002; 99:754–758. PMID: 11806974.
5. Weng WK, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003; 21:3940–3947. PMID: 12975461.
6. Dall'Ozzo S, Tartas S, Paintaud G, Cartron G, Colombat P, Bardos P, et al. Rituximab-dependent cytotoxicity by natural killer cells: influence of FCGR3A polymorphism on the concentration-effect relationship. Cancer Res. 2004; 64:4664–4669. PMID: 15231679.
7. Shin YK, Choi EY, Kim SH, Chung J, Chung DH, Park WS, et al. Expression of leukemia-associated antigen, JL1, in bone marrow and thymus. Am J Pathol. 2001; 158:1473–1480. PMID: 11290565.
8. Chung JK, So Y, Hong MK, Choi SR, Jeong JM, Lee DS, et al. In vitro and in vivo properties of murine monoclonal antibody for a novel immature thymocyte-differentiated antigen, JL1. Nucl Med Biol. 1997; 24:433–437. PMID: 9290079.
9. Park WS, Bae YM, Chung DH, Kim TJ, Choi EY, Chung JK, et al. A cell surface molecule, JL1; a specific target for diagnosis and treatment of leukemias. Leukemia. 1998; 12:1583–1590. PMID: 9766503.
10. Shin YK, Choi YL, Choi EY, Kim MK, Kook MC, Chung J, et al. Targeted cytotoxic effect of anti-JL1 immunotoxin against a human leukemic cell line and its clinical implications. Cancer Immunol Immunother. 2003; 52:506–512. PMID: 12768327.
11. Jeon YK, Min HS, Lee YJ, Kang BH, Kim EJ, Park HJ, et al. Targeting of a developmentally regulated epitope of CD43 for the treatment of acute leukemia. Cancer Immunol Immunother. 2011; 60:1697–1706. PMID: 21710258.
12. Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012; 12:278–287. PMID: 22437872.
13. Tibes R, Keating MJ, Ferrajoli A, Wierda W, Ravandi F, Garcia-Manero G, et al. Activity of alemtuzumab in patients with CD52-positive acute leukemia. Cancer. 2006; 106:2645–2651. PMID: 16688777.
14. Raetz EA, Cairo MS, Borowitz MJ, Blaney SM, Krailo MD, Leil TA, et al. Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: a Children's Oncology Group Pilot Study. J Clin Oncol. 2008; 26:3756–3762. PMID: 18669463.
15. Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016; 375:740–753. PMID: 27292104.
16. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017; 376:836–847. PMID: 28249141.
17. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al. WHO classification of tumours of hematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press;2016.
Full Text Links
  • ALM
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr