Chromosome abnormalities in advanced stage T‐cell lymphoblastic lymphoma of children and adolescents: a report from Japanese Paediatric Leukaemia/Lymphoma Study Group (JPLSG) and review of the literature

Abstract

Summary T‐cell acute lymphoblastic leukaemia (T‐ALL) and T‐cell lymphoblastic lymphoma (T‐LBL) are combined into one category as T lymphoblastic leukaemia/lymphoma in the current World Health Organization (WHO) classification. However, there is still ongoing discussion on whether T‐ALL and T‐LBL are two separate entities or represent two variant phenotypes of the same disease. Cytogenetic analysis has been used to identify the molecular background of haematological malignancies. To compare the distribution of chromosomal abnormalities of T‐ALL and T‐LBL, large series of cytogenetic data are required, but are absent in T‐LBL in contrast to the abundant data in T‐ALL. Among 111 T‐LBL cases in our clinical trial, we obtained complete cytogenetic data from 56 patients. The comparison between our cytogenetic findings and those from three published T‐LBL studies revealed no significant difference. However, meta‐analysis showed that translocations involving chromosome region 9q34 were significantly more common in T‐LBL than in T‐ALL. In particular, four out of the 92 T‐LBL cases, but none of the 523 paediatric T‐ALL cases, showed translocation t(9;17)(q34;q22–23) (P = 0·0004). Further studies are needed for the possible linkage between abnormal expression of genes located at 9q34 and/or 17q22–23 and the unique ‘lymphoma phenotype’ of T‐LBL.

A childhood chemotherapy protocol improves overall survival among adults with T-lymphoblastic lymphoma

“…The outcome with the hyper-CVAD regimen in LBL was first reported by Thomas et al [2], while Sekimizu et al reported that among their patients, 30 (91%) achieved CR, and 3 (9%) achieved PR [5]. But it appears that in our study patients treated with the hyper-CVAD regimen had a poorer prognosis, which may be explained by the too small sample size.…”

“…Cytogenetic abnormalities show no prognostic value in adult, though they are related to an aggressive clinic course. No chromosomal or molecular abnormalities have been consistently shown to carry prognostic significance except t (9;17) (q34;3), which is associated with an aggressive clinical course in children [4, 5]. …”

Molecular genetics related to non-Hodgkin lymphoma

“…About 56-69% abnormal karyotypes, with 3-5% hyperdiploid, 25-44% pseudodiploid and 22-25% hyperdiploid were shown in both T-LBL and T-ALL [38].…”

“…Many of the oncogenes associated with T-ALL, such as NOTCHI, ABL1, SET and NUP214 also exists in 9q34. Thus, it is reasonable that translocation involving 9q34 are more common in T-ALL than T-LBL [38]. The gene FBXW7 is closely related to NOTCHI mutation.…”

Clinical Significance of HOX11L2 and HOX11 Gene Expression in T-ALL Patients

“…HOX11 is aberrantly expressed in childhood T-ALL as a result of either two chromosomal translocations, t(7;10)(q35;q24) and t(10;14)(q24;q11) which place the HOX11 coding sequence under the transcription control of T-cell receptor regulatory elements. HOX11L2 is involved in a cryptic translocation, t(5;14)(q35;q32), detected only by FISH resulting in its ectopic transcription (10,14) . The aim of this study was to determine the prognostic value of two structurally related homeobox genes TLX1/HOX11 and TLX3/HOX11L2 on the clinical outcome of T-ALL patients.…”