Cancer Research | Ricerc@Sapienza

NOTCH1 is aberrantly activated in chronic lymphocytic leukemia hematopoietic stem cells

To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38-HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38-and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors.

IL7R overexpression in adult acute lymphoblastic leukemia is associated to JAK/STAT pathway mutations and identifies patients who could benefit from targeted therapies

The IL7 receptor a chain, encoded by the IL7R gene, heterodimerizes
with the IL-2Rc (common gamma) chain to
form the IL7 receptor, or with the cytokine receptor-like
factor 2 (CRLF2) for the thymic stromal lymphopoietin
(TSLP) receptor, in both B and T cells . Signals from
the IL7 and TSLP receptors activate the JAK/STAT and
PI3K/Akt/mTOR pathways, and are essential for the normal
development and maintenance of the immune system

Refined karyotype-based prognostic stratification of chronic lymphocytic leukemia with a low- and very-low-risk genetic profile

non applicabile, non è previsto abstract.

Lymphomatoid granulomatosis and large granular lymphocyte leukemia, a rare association of two lymphoproliferative disorders

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MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors

MRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity is essential to control faithful DNA replication and to prevent accumulation of deleterious DNA double-strand breaks. In humans, hypomorphic mutations in these genes lead to DNA damage response (DDR)-defective and cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects the nervous system, where MRE11 is required to restrain MYCN-dependent replication stress, during the rapid expansion of progenitor cells.