Publication Only: Chronic lymphocytic leukemia and related disorders - Biology & translational research
B-cell chronic lymphocytic leukemia (CLL) is the most common haematological malignancy in advanced age. The clinical course of the disease is highly variable, therefore there is a need to investigate the various prognostic factors. The transmembrane receptor tyrosine kinase-like orphan receptor 1 (ROR1) is upragulated in chronic lymphocytic leukemia (CLL) cells. ROR1 has a special expression on CLL as a diagnostic marker.
The aim of this study was to compare the relationship between expression of ROR on CLL cells and clinical / laboratory features of CLL patients.
Between February 2010 and June 2018, 30 cases diagnosed with CLL were analyzed. CLL cases were divided into 2 different groups as high (HrROR1) or low (LrROR1) ROR1 expression according to flow cytometric analysis at initial diagnosis. Clinical and laboratory findings of 2 groups were compared during the mean follow-up period of 19 months. Statistical analyzes were performed using chi-square test using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). A value of less than 0.05 was considered significant. Receiver operating characteristic (ROC) curves were formulated to estimate a cut-off of ROR 1 for advanced stage disease. A two- sided p value < 0,05 was considered statistically significant.
The clinical and laboratory data of 30 CLL patients with a median age of 60 (37-83) years and with Female/Male ratio of 16/14 were evaluated. Mean follow-up time was 38.5 (SD ± 34.1) months. One patient (3.3%) died during follow-up. The number of cases with RAI stage 0-1, stage 2, stage 3-4 was 14 (46.7%), 11 (36.6%) and 5 (16.7%). The CD 38 positivity of the patients was 10% with flow cytometry analysis. ROC were used to obtain cut-off levels of ROR1 positivity for RAI stage (early versus intermediate+high). We established a cut-off level of 60% for ROR1 percentage in these subjects for intermediate + high RAI stage (p: 0.032). The calculated cut-off levels had the highest sensitivity compared to the other cut-off levels. The ROC area for percentage of ROR1 was 0,73 with a cutoff value of 60% of ROR1 positivity. The sensitivity and specificity was 92.9% and 62.5%, respectively (figure 1). The count of high rate of ROR1(HrROR1) positivity patients were 20 (66.7%) cases. The clinical and laboratory findings of HrROR1 patients and LrROR1 positivity patients were compared each other (Shown in Table 3). HrROR 1 positivity was associated with presence of splenomegaly (p = 0.011), presence of anemia (p = 0.002) and high beta 2 microglobulin value ≥3 mg/dL and the need for first line treatment (p = 0.029). In 5 out of the 12 patients who had anemia at the initial diagnosis, anemia was related with involvement of CLL. When 7 patients whose anemia is not associated with CLL disease involvement were excluded, HrROR 1 positivity was still associated with the presence of anemia (p = 0.046). All patients in need of first line treatment were in the patient group with HrROR1 positivity.
In our CLL patients, higher rate of ROR1(HrROR1) positivity is related to presence of splenomegaly, presence of anemia, beta 2 microglobulin value ≥3 mg/dL, having RAI Stage 2/3/4 disese and need for first line treatment.