0 1988 S.Karger AG, Basel 0042-9007/88/0541-0057 $2.75/0 Vox Sang. 54: 57-58 (1 988)

HLA-Cw4 Association with Acute Lymphoblastic Leukaemia in Sicilian Patients

Calogero Caruso, Giovanna Cammarata, Guido Sireci, Maria Assunta Modica Servizio di Immunologia Tissutale, Istituto di Patologia generale dell’Universita di Palermo, Italia

Abstract. The HLA frequencies of 50 Sicilian patients affected with acute lymphoblastic leukaemia (ALL) were examined. The frequency of Cw4 antigen was significantly increased in patients. Thus results obtained in our homogeneous population confirm in part previous reports suggesting that CwCrelated genetic factors might be involved in the susceptibility to aetiological or pathogenetic mechanisms which play a role in some haematological malignancies.

Introduction

Recently, frequencies of HLA-A,B,C,DR antigens were analysed in 1,009 leukaemia patients, all of whom had been treated with bone marrow transplantation and reported to the International Bone Marrow Transplant Registry. Cw3 and Cw4 were significantly associated with acute leukaemia [ 11. In the present study we have ana- lysed HLA frequencies of 50 Sicilian patients affected with acute lymphoblastic leukaemia (ALL) to evaluate whether, in our homogeneous population, ALL is asso- ciated with Cw3 and Cw4 antigens.

Materials and Methods

The HLA frequencies of 50 Sicilian patients (23 females and 27 males, mean age 12 f 8) affected with ALL were examined. Most patients (n = 42) were affected with non-B, non-T acute lymphoblas- tic leukaemia. The patients and their relatives had been typed for HLA-A,B,C,DR,DQ antigens in search for an HLA identical bone marrow transplant donor with the use of well-characterized and already applied typing reagents [2-91. HLA-A,B,C antigens had been determined using a set of 120 alloantisera [lo]; HLA-DR, DQ anti- gens had been determined by the two-colour fluorescence assay using 60 alloantisera [ 1 11. According to international suggestions about bone marrow transplantation, most lymphoblastic patients were referred to our department in search of a bone marrow donor because of relapses.

Patient HLA frequencies were compared with those of a sample of the normal Sicilian population (n = 200). For evaluation of HLA association the x z test with Yate’s continuity correction and Fisher’s

exact test were used where appropriate. Probability values (p) were corrected for the total number of antigen comparison (n = 72) using the method of Edwards and then termed pc. Relative risk (RR) was calculated according to the suggested formula [ 12, 131.

Results and Discussion

No significant deviation in HLA-A,B antigen frequen- cies was found in our patients. The distribution of HLA-C antigens frequencies in patients and controls is shown in table I. The frequency of Cw4 antigen was significantly increased in patients affected with ALL (p<0.05; RR =

2.12). The p value was not corrected for the total number of antigens since we looked a priori for the association between Cw4 and leukaemia. As regards HLA-DR,DQ antigen frequencies, HLA-DQw3 frequency was de- creased in ALL patients, but pc value was not significant (data not shown).

Thus our results show that in our homogeneous Cau- casian population there is an increased frequency of Cw4 antigen in ALL-affected subjects. Our data confirm in part previous results of d’Amaro et al. [ 11 which showed that Cw3 and Cw4 antigens were increased in patients affected with acute leukaemia (in our study patients affected by non-lymphoblastic leukaemia were not inves- tigated). As discussed by D’Amaro et al. [ 11 the associa- tion between Cw3 and Cw4 antigens and acute leukae- mias suggests that these antigens may be markers for leukaemia susceptibility gene(s), gene(s) that code(s) for

58 Caruso/Cammarata/Sireci/Modica

Table I. Frequencies of HLA-C antigens in Sicilian patients affected with ALL

Antigen Controls All

n + YO n + YO

Cwl 200 13 6.50 50 4 8.00 Cw2 200 27 13.50 50 5 10.00 Cw3 200 27 13.50 50 3 6.00 cw4 200 54 27.00 50 22 44.00* Cw5 152 8 5.26 50 2 4.00 Cw6 145 20 13.79 50 4 8.00 Cw7 115 14 12.17 50 3 6.00

* p<0.05.

low immune responsiveness to putative leukaemia vi- rus(es) or genes that reguLate(s) the response to chemo- therapy and, therefore, the attainment of remission. (Most of patients studied by D’Amaro et al. [ I ] were transplanted during remission.)

However, the results obtained so far seem to be of some interest since in our homogeneous population, Cw4 antigen frequency was also increased in a sample of patients affected with Hodgkin lymphoma [14, and in preparation]. These data taken together suggest that Cw4- related genetic factors might be involved in the suscepti- bility to aetiological or pathogenetic mechanisms which play a role in some haematological malignancies.

Acknowledgements

This work was supported in part by grant from MPI (Rome, 60%). We wish to thank Prof. Alfred0 Salerno for his helpful criticism.

References

1 D’Amaro, J.; van Rood, J. J.; Bach, F. H., Rimm, A. A.; Bortin, M. M.: HLA-C associations with acute leukaemia. Lancet ii:

2 Caimi, G.; Galluzzo, A,; Giordano, C.; Caruso, C.; Capobianco, D.; Sarno, A.: Genetic pattern and haemorheological determi- nants in type 1 diabetics. Clin. Hemorheol. 5: 155-158 (1985).

1176-1 178 (1984).

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Caruso, C.; Bellina, L.: B8,DR3 antigens and production of human leucocyte migration inhibitory factor (LIF) by mononu- clear cells stimulated with concanavalin A (Con-A). Tissue Anti- gens 22: 167- 169 ( 1 983). Caruso, C.; Oliva, L.; Palmeri, P.; Cottone, M.: B-cell alloanti- gens in Sicilian patients with Crohn’s disease. Tissue Antigens 21:

Caruso, C.; Lio, D.; Palmeri, P.; Cillari, E.: HLA-DR phenotypes and blood levels of T cells subset. Tissue Antigens 24: 320-322 (1 984). Caruso, C.; Cillari, E.; Palmeri, P.; Lio, D.; Salerno, A.: OKT4+ and OKT8+ cell subset values and HLA-DR phenotypes. J. clin. Lab. Immunol. 16: 91-92 (1985). Caruso, C.; Palmeri, P.; Oliva, L.; Orlando, A.; Cottone, M.: HLA antigens in ulcerative colitis: a study in the Sicilian population. Tissue Antigens 25: 47-49 (1985). Gallina, G.; Cumbo, V.; Messina, P.; Caruso, C.: HLA- A,B,C,DR,MT and MB antigens in recurrent aphthous stomati- tis. Oral Surg., oral Med., oral Path. 59: 364-370 (1985). Gallina, G.; Cumbo, V.; Messina, P.; Modica, M. A,; Caruso, C.: MHC-linked genetic factors (HLA B3 5) influencing recurrent circumoral herpetic lesions. Dis. Markers (in press). van Rood, J. J.: Microlymphocytotoxicity method; in Ray, Man- ual of tissue typing techniques, pp. 104-105 (NIH, Bethesda 1979). van Leeuwen, A.; van Rood, J. J.: Description of Bcell methods; in Terasaki, Histocompatibility testing 1980, pp. 278-279 (UCLA Tissue typing laboratory, Los Angeles 1980). D’Amaro, J.: HLA polymorphism in the Netherlands. A study in population and immunogenetics; thesis Leiden (1978). Moller, G.: HLA and disease susceptibility. Immunol. Rev. 70 (1983). Caruso, C.; Modica, M.A.; Palmeri, P.; Valenti, A.; Tambone Reyes, M.; Di Marco, P.; Citarrella, P.: Associazione tra gli antigeni del sistema maggiore di istocompatibilita e linfoma di Hodgkin in un campione di pazienti della Sicilia Occidentale; in Attualita. in Ematologia. XXX Congr. Naz. SOC. Ital. Emat., pp. 8 17-820 (Monduzzi Editore, Bologna 1985).

170-171 (1983).

Received: May 11, 1987 Revised manuscript received: June 24, 1987 Accepted: June 24, I987

Calogero Caruso, MD Servizio di Immunologia Tissutale Istituto di Patologia generale Corso Tukory 2 1 1 1-901 34 Palermo (Italy)