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.
BACKGROUND
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.
Wang
Liang
L
Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, 510632, PR China.
Zhu
Kanger
K
Zha
Xianfeng
X
Chen
Shaohua
S
Yang
Lijian
L
Chen
Si
S
Li
Yangqiu
Y
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D002648:Child; D002999:Clone Cells; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007372:Interferons / Q000008:administration & dosage; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics*; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000068877:Imatinib Mesylate; D007372:Interferons