Detection of trisomy 12 in chronic lymphocytic leukemia: association with CD 38 and clinical outcome

ABSTRACT

Staging systems and laboratory features help predict survival in chronic lymphocytic leukemia [CLL], but they don't distinguish patients who will progress from those whose disease will remain indolent. Trisomy 12 is one of the most common chromosomal abnormalities in B-CLL, but has also been found in a substantial proportion of cases with other chronic leukemic B-cell disorders, such as lymphoplasmacytoid lymphomas. There are contradicting reports on the prognostic importance of trisomy 12 in some reports the abnormality has been associated with a poor prognosis, while in others no inferior survival was seen in patients with trisomy 12 positive CLL. This prompted us to assess its prognostic significance and to evaluate its frequency and clinical characteristics in patients with B-CLL. Twenty patients at different Rai's stages of CLL were included in the current study, their mean age was 54.8 years, with a male to female ratio 13 7. Peripheral blood smears and bone marrow aspirate smears were collected from each patient. Cytologic preparations were examined microscopically in order to assess the lymphocyte morphology. Immunophenotyping was performed. The diagnosis was supported in all cases by histologic findings in bone marrow biopsy and lymph node biopsy specimens. All patients were subjected to complete history, thorough clinical examination and laboratory investigations, including complete hemogram, bone marrow examination and Immunophenotyping Detection of chromosome 12 was assessed by conventional cytogenetic analysis [CCA] and fluorescence in situ hybridization [FISH] on PB or BM samples to evaluate the two methods. Follow-up of patients was carried out by clinical signs, symptoms, BM examination and response to therapy to detect the outcome of the disease. Molecular study using FISH revealed that the overall incidence of trisomy 12 in CLL studied cases was 20% [4 / 20]. CCA revealed only 2 positive cases. Two patients with trisomy 12 had received previous treatment. In patients containing this molecular abnormality, initial WBCs count more than 50 x 10[9] /L, Hb level less than 9 g/dL, high peripheral lymphocyte count were significantly different than those lacking it [P <0.05] Patients with trisomy 12 revealed a significant difference from those who were negative as regard the clinical outcome [P <0.05]. CD38 identifies a surface molecule with multifunctional activity. Its prognostic importance in B-CLL is currently under investigation in view of the fact that two different groups have recently indicated that CD38 expression could be an independent prognostic marker in B-CLL. In the present work 9 [45%] patients expressed CD38 in more than 20% of CD19 positive cells and were considered as CD38 positive B-CLL. Trisomy 12 was detected more frequently in the CD38 positive B-CLL group. These findings implied that trisomy 12 conferred a poor prognosis for this subgroup of patients