TCL1A gene involvement in T-cell prolymphocytic leukemia in Japanese patients

Abstract

T-cell prolymphocytic leukemia (T-PLL) is a rare type of peripheral T-cell leukemia. In this study, we examined the clinical and biological characteristics of 11 Japanese patients with T-PLL. Median age was 74 years, with male predominance. Median lymphocyte frequency was 85.3% in blood. Physical characteristics were splenomegaly (36.4%), tiny lymph adenopathy (63.6%), skin lesion (9.1%) and pleural effusion (27.3%). Median survival was 30.1 months, despite treatment with various chemotherapeutic modalities. Although complex chromosomal abnormalities were observed in 5 of 11 cases (45.5%), typical 14q32 and Xq28 abnormalities were not detected. TCL1A mRNA expression was observed in 6 of 11 cases (54.5%) on real-time quantitative PCR. In 5 of these 6 cases, flow cytometric analysis and/or immunohistochemistry confirmed the expression of TCLA1 protein. Split signals for the TCL1 region on fluorescence in situ hybridization confirmed rearrangement in 3 out of 7 cases evaluated. These cases corresponded to cases that were positive for TCL1A expression, suggesting that rearrangement of the TCL1 region induced high expression of TCL1A gene. In summary, a substantial number of T-PLL cases in Japan had abnormal expression of TCL1A, probably due to rearrangement of TCL1 region. Expression and/or rearrangement of TCL1A may, therefore, be a useful marker for diagnosing T-PLL, regardless of chromosomal abnormalities.

Comparison of clinicopathological characteristics between T‐cell prolymphocytic leukemia and peripheral T‐cell lymphoma, not otherwise specified

“…Although the male-to-female ratios and medians in this study were consistent with those of previous studies, 1,17,18 of T-PLL patients in the present study were 60.9 months and 57.5%, respectively. These results are similar to those previously reported in Japanese patients.…”

“…Although the male‐to‐female ratios and medians in this study were consistent with those of previous studies, the frequencies of clinical manifestations including CNS involvement, hepatomegaly, splenomegaly, and pleural effusion were much lower than previously reported in patients of a Western country by Matutes et al . Moreover, while the median survival of T‐PLL patients in the United Kingdom and the United States in 2002 was reported to be less than 12 months despite the administration of alemtuzumab (Campath‐1H) for relapsed/refractory cases, the median survival and 5‐year OS of T‐PLL patients in the present study were 60.9 months and 57.5%, respectively.…”

“…These results are similar to those previously reported in Japanese patients. 17,18 Additionally, some cases showing indolent clinical courses have also been reported in Western countries. 20,21 Improvements in supportive therapies including antibiotics, antifungal drugs, antiviral drugs, and granulocyte-colony-stimulating factor might contribute to improved prognosis.…”

Comparison of karyotyping,TCL1fluorescence in situ hybridisation and TCL1 immunohistochemistry in T cell prolymphocytic leukaemia

“…It is known that TCL1 is negative in normal T cells, and TCL1 rearrangement is absent in various other types of T cell neoplasms 8. TCL1 protein expression was reported to be absent in T cell neoplasms other than T-PLL in a small series 28. We performed TCL1 IHC on seven PTCL cases with BM and PB involvement; all were negative (data not shown).…”

“…It is noteworthy that subset expression (in <30% tumour cells) was observed in 8/51 (16%) cases, including 2 cases where FISH was performed showing TCL1 rearrangement in most of the tumour cells. Different levels of TCL1 expression have been observed in T-PLL by real-time quantitative PCR28 or by IHC 6. A high level of TCL1 oncoprotein expression has been associated with a higher WBC count at presentation, faster tumour cell doubling and enhanced in vitro growth response to T cell receptor engagement 6.…”