Deepali Pal
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View article: Protocol for in vitro co-culture, proliferation, and cell cycle analyses of patient-derived leukemia cells
Protocol for in vitro co-culture, proliferation, and cell cycle analyses of patient-derived leukemia cells Open
Leukemia niche impacts quiescence; however, culturing patient-derived samples ex vivo is technically challenging. Here, we present a protocol for in vitro co-culture of patient-derived xenograft acute lymphoblastic leukemia (PDX-ALL) cells…
View article: A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing
A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing Open
Patient derived xenograft (PDX) models are regarded as gold standard preclinical models in leukaemia research, especially in testing new drug combinations where typically 45-50 mice are used per assay. 9000 animal experiments are performed…
View article: Susceptibility of pediatric acute lymphoblastic leukemia to STAT3 inhibition depends on p53 induction
Susceptibility of pediatric acute lymphoblastic leukemia to STAT3 inhibition depends on p53 induction Open
Advances in the clinical management of pediatric B cell Acute Lymphoblastic Leukemia (B-ALL) have dramatically improved outcomes for this disease. However, relapsed and high-risk disease still contribute to significant numbers of treatment…
View article: Tunnelling nanotubules are druggable mediators of cancer-niche crosstalk
Tunnelling nanotubules are druggable mediators of cancer-niche crosstalk Open
Treatment resistance, conferred onto cancer cells largely by the oncogenic niche, remains a clinically unmet need in leukaemia. Tractable and clinically translatable models that mimic cancer-niche crosstalk remain limited, consequently mea…
View article: Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia
Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia Open
This review discusses current research on acute paediatric leukaemia, the leukaemic bone marrow (BM) microenvironment and recently discovered therapeutic opportunities to target leukaemia–niche interactions. The tumour microenvironment pla…
View article: A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing
A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing Open
Patient derived xenograft (PDX) models are regarded as gold standard preclinical models in leukaemia research, especially in testing new drug combinations where typically 45-50 mice are used per assay. 9000 animal experiments are performe…
View article: Epigenetic regulator genes direct lineage switching in <i>MLL/AF4</i> leukemia
Epigenetic regulator genes direct lineage switching in <i>MLL/AF4</i> leukemia Open
The fusion gene MLL/AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukemia. Relapse can be associated with a lineage switch from acute lymphoblastic to acute myeloid leukemia, resulting in poor clinical outcomes caused by re…
View article: A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing
A human mesenchymal spheroid prototype to replace moderate severity animal procedures in leukaemia drug testing Open
Patient derived xenograft (PDX) models are regarded as gold standard preclinical models in leukaemia research, especially in testing new drug combinations where typically 45-50 animals are used per assay. 9000 animal experiments are perfor…
View article: Direct targeted therapy for MLL‐fusion‐driven high‐risk acute leukaemias
Direct targeted therapy for MLL‐fusion‐driven high‐risk acute leukaemias Open
Background Improving the poor prognosis of infant leukaemias remains an unmet clinical need. This disease is a prototypical fusion oncoprotein‐driven paediatric cancer, with MLL ( KMT2A )‐fusions present in most cases. Direct targeting of …
View article: Epigenetic regulator genes direct lineage switching in <i>MLL-AF4</i> leukaemia
Epigenetic regulator genes direct lineage switching in <i>MLL-AF4</i> leukaemia Open
The fusion gene MLL-AF4 defines a high-risk subtype of pro-B acute lymphoblastic leukaemia. However, relapse can be associated with a switch from acute lymphoblastic to acute myeloid leukaemia. Here we show that these myeloid relapses shar…
View article: Human bone marrow milieu identifies a clinically actionable driver of niche-mediated treatment resistance in leukaemia
Human bone marrow milieu identifies a clinically actionable driver of niche-mediated treatment resistance in leukaemia Open
Leukaemia cells re-program their microenvironment to provide proliferation support and protection from standard chemotherapy, molecularly targeted therapies, and immunotherapy. Although much is becoming known about molecules that drive nic…
View article: Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL
Impaired Condensin Complex and Aurora B kinase underlie mitotic and chromosomal defects in hyperdiploid B-cell ALL Open
B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, and high-hyperdiploidy (HyperD) identifies the most common subtype of pediatric B-ALL. Despite HyperD is an initiating oncogenic event affiliated to childhood…
View article: PF161 THIOREDOXIN SYSTEM INHIBITORS ARE EFFECTIVE AGAINST B CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN VITRO AND IN VIVO
PF161 THIOREDOXIN SYSTEM INHIBITORS ARE EFFECTIVE AGAINST B CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN VITRO AND IN VIVO Open
Background: B‐cell acute lymphoblastic leukemia (B‐ALL) is a heterogeneous hematological disorder characterized by accumulation of B cell precursors. Although undeniable improvement has been made in the therapy of B‐ALL (>90% of pediatric …
View article: The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation
The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation Open
(Cancer Cell 34, 626–642.e1–e8; October 8, 2018) During the preparation of the manuscript, we inadvertently left out Dr. Cameron Osborne, who was an important contributor to the chromatin capture experiments described in our article. His c…
View article: Targeting the thioredoxin system as a novel strategy against B‐cell acute lymphoblastic leukemia
Targeting the thioredoxin system as a novel strategy against B‐cell acute lymphoblastic leukemia Open
B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) is a genetically heterogeneous blood cancer characterized by abnormal expansion of immature B cells. Although intensive chemotherapy provides high cure rates in a majority of patients…
View article: Differentiation of Human Embryonic Stem Cells to Sympathetic Neurons: A Potential Model for Understanding Neuroblastoma Pathogenesis
Differentiation of Human Embryonic Stem Cells to Sympathetic Neurons: A Potential Model for Understanding Neuroblastoma Pathogenesis Open
Background and Aims . Previous studies modelling human neural crest differentiation from stem cells have resulted in a low yield of sympathetic neurons. Our aim was to optimise a method for the differentiation of human embryonic stem cells…
View article: The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation
The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation Open
Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but highly challenging therapeutic targets. We used epigenomic profiling data for …
View article: Inhibition of ATR acutely sensitizes acute myeloid leukemia cells to nucleoside analogs that target ribonucleotide reductase
Inhibition of ATR acutely sensitizes acute myeloid leukemia cells to nucleoside analogs that target ribonucleotide reductase Open
Key Points Loss of ATR signaling is cytotoxic to AML cells in combination with gemcitabine and hydroxyurea via the induction of replication stress. A small molecule inhibitor of ATR in combination with gemcitabine completely eradicates AML…
View article: Temporary Single-Cell Coating for Bioprocessing with a Cationic Polymer
Temporary Single-Cell Coating for Bioprocessing with a Cationic Polymer Open
Temporary single-cell coating is a useful tool for cell processing, allowing manipulation of cells to prevent cell attachment and agglomeration, before re-establishing normal cell function. In this work, a speckled coating method using a k…