Acute lymphoblastic leukemia (ALL) and myeloid malignancies.

This translocation is likely to be molecularly heterogeneous.

Only one case to date with identification of ETV6 and TTL as genes involved in the translocation : a 46 year-old male patient with ALL (blasts were CD10+/-, CD19+) (Qiao et al., 2003)..

Altogether, 15 cases are available:
Pre-B or early pre-B ALL cases, with an unbalanced sex ratio (7M/2F), and a median age of 6 years (range: 2-46), 7 of 9 patients being children (Raimondi et al., 1989; Pui et al., 1991; Raimondi et al., 1991; Chan et al., 1994; Kobayashi et al., 1994; Raimondi et al., 1997; Coignet et al., 1999; Qiao et al., 2003).
Myeloid cases: 1 chronic myelomonocytic leukaemia (CMML), 1 chronic myelogenous leukaemia in blast crisis (BC-CML), 1 M3 acute myeloid leukaemia (AML), 1 M0-AML, and 2 treatment related AML (t-AML). In contrast with lymphoid cases, the sex ratio was balanced (3M/3F), and median age was 58 years (range (51-70) (Zitzelsberger et al., 1990; Abeliovich et al., 1993; Fugazza et al., 1997; Tosi et al., 1998; Castro et al., 2000; Temperani et al., 2000).

The patient with ETV6/TTL hybrid gene attained complete remission, but relapsed and died of refractory disease 4 years after diagnosis.

Both reciprocal transcripts, TTL/ETV6 and ETV6/TTL, were detected. ETV6/TTL fusion transcript comprises 5 ETV6 exon 1, fused to TLL exon 9, resulting in a potential 31 amino acids peptid.
The other transcript, TTL/ETV6, comprises 5 TTL exons 1 to 5 or to 8a, fused to ETV6 from exon 2. The predicted 530 amino acids fusion protein consists mostly of ETV6 with both HLH and ETS domains, and could have modified transcriptional activities. On the other hand, a loss of function of ETV6 and/or of TTL could play the critical role in leukemogenesis.