Disease relevance of Hlf

• The hepatic leukemia factor (HLF) gene codes for a basic region-leucine zipper (bZIP) protein that is disrupted by chromosomal translocations in a subset of pediatric acute lymphoblastic leukemias [1].

High impact information on Hlf

• To identify physiologic counterparts of this chimera, we investigated the function of other bZIP factors that bind to the same DNA sequence recognized by E2A-HLF [2].
• Here, we show that thyrotroph embryonic factor (TEF), which shares a high level of sequence identity with HLF and recognizes the same DNA sequence, is expressed in a small fraction of each subset of hematolymphoid progenitors [2].
• In the spleen, mature T cells were present but in reduced numbers, and they lacked expression of the transgene, suggesting further that E2a-Hlf expression was incompatible with T-cell differentiation [1].
• Within the thymus, E2a-Hlf induced profound hypoplasia, premature involution, and progressive accumulation of a T-lineage precursor population arrested at an early stage of maturation [1].
• In contrast, mature splenic B cells expressed E2a-Hlf but at lower levels and without apparent adverse or beneficial effects on their survival [1].

Biological context of Hlf

• Hlf expression was not associated with cells undergoing programmed cell death in the nervous system [3].
• TEF, an antiapoptotic bZIP transcription factor related to the oncogenic E2A-HLF chimera, inhibits cell growth by down-regulating expression of the common beta chain of cytokine receptors [2].

Anatomical context of Hlf

• Subsequently, Hlf expression increased in the central nervous system and was found throughout the brain by adulthood [3].
• During embryonic brain development, Hlf expression was restricted to the anterior pituitary and meninges [3].
• In the developing pituitary gland, Hlf was highly expressed in the rostral tip of the anterior lobe [3].
• By early postnatal life, Hlf was highly expressed in somatosensory cortex, thalamic nuclei, and structures arising from ectodermal placodes [3].
• When introduced into NIH 3T3 cells in a zinc-inducible vector, each of these mutants induced anchorage-independent growth as efficiently as unaltered E2A-HLF, indicating that the chimeric oncoprotein can transform cells in its homodimeric form [4].

Other interactions of Hlf

• This pattern is similar to that of Tef, an Hlf-related bZIP protein [3].

Analytical, diagnostic and therapeutic context of Hlf

• Therefore, we cloned mouse Hlf and studied its expression by in situ hybridization [3].

References