Daniel Sasca
Wellcome Trust
HaematopoiesisProgenitor cellImmunologyMyeloid leukemiaMedicine
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Publications 9
#1Haiyang Yun (Heidelberg University)
#2Shabana Vohra (University of Cambridge)H-Index: 2
Last. Ludovica Marando (University of Cambridge)H-Index: 2
view all 19 authors...
Altered transcription is a cardinal feature of acute myeloid leukemia (AML), however, exactly how mutations synergize to remodel the epigenetic landscape and rewire 3-Dimensional (3-D) DNA topology is unknown. Here we apply an integrated genomic approach to a murine allelic series that models the two most common mutations in AML, Flt3-ITD and Npm1c. We then deconvolute the contribution of each mutation to alterations of the epigenetic landscape and genome organization, and infer how mutations sy...
#1Haiyang Yun (University of Cambridge)H-Index: 5
Last. Ludovica Marando (University of Cambridge)H-Index: 2
view all 17 authors...
#1Daniel Sasca (Wellcome Trust)H-Index: 3
#2Haiyang Yun (University of Cambridge)H-Index: 5
Last. Brian J. P. Huntly (University of Cambridge)H-Index: 43
view all 16 authors...
Cohesin complex disruption alters gene expression and Cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore Cohesin dynamics and regulation of hematopoietic stem cell homeostasis and differentiation. Cohesin binding increases at active regulatory elements only during erythroid differentiation. Prior binding of the repressive Ets transcription factor Etv6 predicts Cohesin binding at these elements and Etv6 interacts with Cohesin at chroma...
1 CitationsSource
#1Faisal Basheer (University of Cambridge)H-Index: 4
#2George Giotopoulos (University of Cambridge)H-Index: 10
Last. Brian J. P. Huntly (University of Cambridge)H-Index: 43
view all 24 authors...
The Huntly laboratory is funded by CRUK (Programme C18680/A25508), ERC (Grant 647685 COMAL), KKLF, MRC, Bloodwise, the Wellcome Trust (WT) and the Cambridge NIHR BRC. F.B. is a recipient of a Wellcome Trust PhD for Clinicians award. P.G. is funded by the Wellcome Trust (109967/Z/15/Z). We acknowledge the WT/MRC centre grant (097922/Z/11/Z) and support from WT strategic award 100140. Research in the laboratory is also supported by core funding from Wellcome and MRC to the Wellcome-MRC Cambridge S...
5 CitationsSource
#1Paolo Gallipoli (University of Cambridge)H-Index: 13
#2George Giotopoulos (University of Cambridge)H-Index: 10
Last. Brian J. P. Huntly (University of Cambridge)H-Index: 43
view all 16 authors...
FLT3 internal tandem duplication (FLT3ITD) mutations are common in acute myeloid leukemia (AML) associated with poor patient prognosis. Although new-generation FLT3 tyrosine kinase inhibitors (TKI) have shown promising results, the outcome of FLT3ITD AML patients remains poor and demands the identification of novel, specific, and validated therapeutic targets for this highly aggressive AML subtype. Utilizing an unbiased genome-wide clustered regularly interspaced short palindromic repeats (CRISP...
15 CitationsSource
#1Sarah J. HortonH-Index: 11
#2George GiotopoulosH-Index: 10
Last. Brian J. P. HuntlyH-Index: 43
view all 31 authors...
Horton et al. show that early Crebbp loss in haematopoietic progenitors results in a defective p53-mediated DNA damage response, leading to the accumulation of epigenetic and genetic alterations, which promote the onset of lymphoid malignancies.
11 CitationsSource
#1Brian J. P. Huntly (University of Cambridge)H-Index: 43
#2Sarah J. Horton (University of Cambridge)H-Index: 11
Last. David H. AdamsH-Index: 103
view all 16 authors...
Loss-of-function mutations of the cyclic-AMP response element binding protein, binding protein (CREBBP) gene have recently been described at high frequencies across a spectrum of lymphoid malignancies, particularly follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). The multiple effects of this epigenetic regulator on developmental and homeostatic processes have been extensively studied, however, exactly how CREBBP functions as a tumor suppressor and the reasons for its particula...
1 CitationsSource
A new study provides the first insights into epigenetic heterogeneity in AML. The study highlights a striking independence of genetic and epigenetic variation, and links the kinetics of epigenetic change to clinical outcome.
3 CitationsSource
#1Daniel Sasca (University of Cambridge)H-Index: 3
#2Andrea Schueler (University of Mainz)H-Index: 1
Last. Thomas Kindler (University of Mainz)H-Index: 23
view all 12 authors...
Background Acute myeloid leukemia (AML) is a heterogeneous disease of the hematopoietic progenitor cell driven by the subsequent acquisition of genetic alterations. Approximately 20% of AML patients show strong expression of CD56 (neural cell adhesion molecule; NCAM). Expression of NCAM is associated with poor overall survival; however, the functional role of aberrant NCAM expression has not been investigated to date. The goal of this study is to examine the biological role of NCAM in AML and to...
1 CitationsSource