Evolution of T-cell clonality in a patient with Ph-negative acute lymphocytic leukemia occurring after interferon and imatinib therapy for Ph-positive chronic myeloid leukemia.

INTRODUCTION: The development of Philadelphia chromosome (Ph) negative acute leukemia/myelodysplastic syndrome (MDS) in patients with Ph-positive chronic myeloid leukemia (CML) is very rare. The features of restrictive usage and absence of partial T cell clones have been found in patients with CML. However, the T-cell clonal evolution of Ph-negative malignancies during treatment for CML is still unknown.

OBJECTIVE: To investigate the dynamic change of clonal proliferation of T cell receptor (TCR) Valpha and Vbeta subfamilies in one CML patient who developed Ph-negative acute lymphoblastic leukemia (ALL) after interferon and imatinib therapy.

METHODS: The peripheral blood mononuclear cells (PBMC) samples were collected at the 3 time points (diagnosis of Ph-positive chronic phase (CP) CML, developing Ph-negative ALL and post inductive chemotherapy (CT) for Ph-negative ALL, respectively). The CDR3 size of TCR Valpha and Vbeta repertoire were detected by RT-PCR. The PCR products were further analyzed by genescan to identify T cell clonality.

RESULTS: The CML patient who achieved complete cytogenetic remission (CCR) after 5 years of IFN-alpha therapy suddenly developed Ph-negative ALL 6 months following switch to imatinib therapy. The expression pattern and clonality of TCR Valpha/Vbeta T cells changed in different disease stages. The restrictive expression of Valpha/Vbeta subfamilies could be found in all three stages, and partial subfamily of T cells showed clonal proliferation. Additionally, there have been obvious differences in Valpha/Vbeta subfamily of T cells between the stages of Ph-positive CML-CP and Ph-negative ALL. The Valpha10 and Vbeta3 T cells evolved from oligoclonality to polyclonality, the Vbeta13 T cells changed from bioclonality to polyclonality, when Ph-negative ALL developed.

CONCLUSIONS: Restrictive usage and clonal proliferation of different Valpha/Vbeta subfamily T cells between the stages of Ph-positive CP and Ph-negative ALL were detected in one patient. These changes may play a role in Ph- negative leukemogenesis.