Vol 3, No 4 (2012)
Review paper
Published online: 2013-01-15

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Deregulation of MYC transcription factor in lymphoid tumors — molecular, pathogenetic, clinical and therapeutic implications

Tomasz Sewastianik, Monika Prochorec-Sobieszek, Przemysław Juszczyński
Hematologia 2012;3(4):313-326.

Abstract

MYC transcription factor is one of the most frequently deregulated oncogenes in human
malignancies. It encodes a leucine zipper transcription factor that controls a broad spectrum of
cellular genes responsible for enhanced proliferation, cellular metabolism, growth, vasculogenesis,
metastasis, genomic instability, stem cell self-renewal and reduced differentiation. In
mouse models, full-blown phenotype of MYC-driven tumors requires cooperation with other
lesions, including p53 pathway mutations, TCF3 mutations, PI3K activity and BCL2 family
abnormalities. In human B-cell tumors, MYC rearrangements involving 8q24 region and
immunoglobulin genes are hallmark of Burkitt lymphoma, but also occur in other lymphoid
malignancies. In diffuse large B-cell lymphoma, MYC is the third, after BCL6 and BCL2,
most commonly deregulated oncogene. Simple MYC/IGH rearrangements in these tumors are
uncommon and more frequently involve light chain or non-IG partners and exist in the setting
of complex karyotypes. The most common cytogenetic abnormality accompanying MYC is
t(14;18) involving BCL2 and less frequently BCL6. Such “double/triple hit” B-cell tumors
harboring BCL2 and/or BCL6 rearrangements concurrent with MYC lesions frequently exhibit
atypical morphologic and/or immunophenotypic features and particularly aggressive clinical
behavior. Given the broad range of MYC functions, inhibition of MYC activity might be
a rational therapeutic strategy in lymphoid tumors expressing this oncogene. Several approaches
for pharmaceutical intervention have been suggested. Herein, we review the molecular
pathogenetic mechanisms associated with MYC deregulation in human B-cell tumors and its
implications for such targeted therapies.

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Hematology in Clinical Practice