Surprisingly however, NHD13 transgenic mice lacking Lyl1 showed accelerated T-ALL and absence of transformation to AML, associated with a loss of multipotent progenitors in the bone marrow.
Our data provide insight into the mechanisms controlling lymphocyte specification and may reveal a basis for the unique functions of Tal1 and Lyl1 in T acute lymphoblastic leukemia.
Thus, the LMO2-LYL1 interaction is a promising therapeutic target for inhibiting self-renewing cancer stem cells in T-ALL, including poor-prognosis ETP-ALL cases.
In hematopoiesis, the two major bHLH factors are stem cell leukemia (SCL) and lymphoblastic leukemia-derived sequence 1 (LYL1), both identified more than 20 years ago in chromosomal translocations occurring in T-cell acute lymphoblastic leukemia.
Molecular characterization of a t(7;19)(q34;p13) in a pediatric T-cell acute lymphoblastic leukemia patient led to the identification of a translocation between the TRB@ and LYL1 loci.
TAL1, LYL1, HOX11 and other transcription factors essential for normal hematopoiesis are often misexpressed in the thymus in T-cell acute lymphoblastic leukemia (T-ALL), leading to differentiation arrest and cell transformation.
LYL1, a member of the class II basic helix-loop-helix transcription factors, is aberrantly expressed in a fraction of human T-cell acute lymphoblastic leukemia.
TAL2 potentially encodes a basic helix-loop-helix motif that is highly related to those specified by TAL1 and LYL1, distinct genes that have also been implicated in T-ALL.
The bHLH domain of TAL1 is especially homologous to those encoded by TAL2 and LYL1, distinct genes that were also identified on the basis of chromosomal rearrangement in T-ALL.
Hence, TAL2, TAL1, and LYL1 constitute a discrete subgroup of helix-loop-helix proteins, each of which can potentially contribute to the development of T-ALL.
The E2A gene is involved by the t(1;19)(q23;p13) in acute pre-B-cell leukemias and the LYL1 gene is structurally altered by a t(7;19)(q34;p13) in T-cell ALL.