Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia.

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.

Prospective study of prognostic factors in asymptomatic patients with B-cell chronic lymphocytic leukemia-like lymphocytosis: the cut-off of 11 × 10(9)/L monoclonal lymphocytes better identifies subgroups with different outcomes.

The arbitrary threshold of 5 × 10(9)/L chronic lymphocytic leukemia (CLL)-like lymphocytes differentiates monoclonal B lymphocytosis (MBL) from CLL. There are no prospective studies that search for the optimal cut-off of monoclonal lymphocytes able to predict outcome and simultaneously analyze the prognostic value of classic, immunophenotypic, and cytogenetic variables in patients with asymptomatic clonal CLL lymphocytosis (ACL), which includes MBL plus Rai 0 CLL patients. From 2003 to 2010, 231 ACL patients were enrolled in this study. Patients with 11q deletion and atypical lymphocyte morphology at diagnosis had shorter progression-free survival (PFS) (p = 0.007 and p = 0.015, respectively) and treatment-free survival (TFS) (p = 0.009 and p = 0.017, respectively). Elevated beta-2 microglobulin (B2M) also correlated with worse TFS (p = 0.002). The optimal threshold of monoclonal lymphocytes independently correlated with survival was 11 × 10(9)/L (p = 0.000 for PFS and p = 0.016 for TFS). As conclusion, monoclonal lymphocytosis higher than 11 × 10(9)/L better identifies two subgroups of patients with different outcomes than the standard cut-off value of 5 × 10(9)/L. Atypical lymphocyte morphology, 11q deletion and elevated B2M had a negative impact on the survival in ACL patients.