Myelodysplastic syndrome (MDS) is a group of clonal blood cell disorders characterized by abnormal-looking cells (cytologic dysplasia) and low cell count (refractory cytopenias) as a result of ineffective blood production (hematopoiesis). About 30-40 percent of MDS cases progress to acute myeloid leukemia (AML), a type of blood cancer, with poor prognosis and short survival time. We have discovered that a novel embryonic stem cell factor also a leukemic stem cell factor SALL4 is involved in the development of MDS and AML. We propose to study the SALL4 pathway in MDS and AML using murine models and test small molecule drugs that can block SALL4 function in MDS/AML. This study will provide new and critical insights and novel pathways in mediating MDS and its progression to AML which will enable us to develop innovative drugs in treating these patients in the near future.
Long Interspersed Element-1 (L1) retrotransposon is the driving force of all transposon-induced mutagenesis in the human genome. L1-induced mutagenesis has taken a center stage after new L1 insertions have been identified in cancer-promoting genes, suggesting that L1 mutations may be driving human cancers. This study is focused on lung cancer because many lung malignancies are deficient in a cellular pathway shown to suppress L1-induced damage in cultured cells. This funding allowed us to develop a reliable pipeline for Next Generation Sequencing analysis of L1 expression. The funding also provided the opportunity to further our understanding of the impact of L1-induced damage in lung cancer in vivo.
Funded by 2012 The V Foundation Wine Celebration and Jimmy V Celebrity Golf Classic
The attacks on the World Trade Center (WTC) on Sept 11, 2001 created an environmental exposure to WTC aerosolized dust and gases that contained known and suspected carcinogens. We continue to prospectively follow the entire FDNY cohort of firefighters and emergency medical service (EMS) workers that were exposed to these carcinogens for cancer incidence and have proposed to conduct studies to estimate the prevalence of blood cancers (myeloma and myelodysplastic syndromes) and pre-cancerous conditions in a subset of this cohort. Studies being conducted at Dr Landgren’s lab at Sloan Kettering are analyzing the proteins in the blood samples for detection of myeloma and pre-myeloma disorders. Studies at Dr Verma’s lab are using genome sequencing technologies to detect for the presence of cancer associated mutations in these samples. Dr Prezant’s group at FDNY has built infrastructure for the collection of the samples and has led to successful banking of over 3000 samples from firefighters exposed to the WTC disaster. Data generated from these studies will uncover the effects of WTC exposure on the development of blood disorders and also demonstrate the role of environmental exposures on cancer in general.
