About the Klco Lab

Myeloid tumors in children are commonly caused by a different set of mutations than those seen in adults, but the genetics of pediatric myeloid tumors are not well understood. Our laboratory is focused on defining the molecular and biological causes of this class of tumors. We build collaborative partnerships and use genomics to identify new classes of mutations that lead to these cancers. Our work aims to transform the diagnosis and management of these diseases in children. 

Science Team

The Team

The Klco Lab has a diverse team including post-doctoral fellows, senior scientific staff, technicians and bioinformaticians collectively focused on studying pediatric myeloid tumors

Our research summary

Uniquely positioned at the interface of basic research and clinical care, our laboratory deciphers the underlying mechanisms of pediatric myeloid tumors. We use genomic sequencing and -omics analyses to identify novel and recurrent mutations coupled with in vitro and in vivo strategies to model and decipher the molecular mechanisms associated with these genetic alterations.  The goal of our research program is to ultimately improve the diagnosis and risk stratification of myeloid tumors and to identify molecular pathways that may be amenable to therapeutic targeting.

Identification of genetic drivers in pediatric myeloid tumors

The myeloid tumors (notably myelodysplastic syndromes and acute myeloid leukemia) that develop in children commonly have a different set of genetic alterations as those seen in adults, yet unlike adults, very little is known about the genetics of pediatric myeloid tumors.  Our laboratory has published landmark studies on core binding factors AMLs , pediatric MDS  and pediatric therapy-related myeloid neoplasms  to comprehensively define the somatic and germline alterations that drive these neoplasms.   Notably, our studies on pediatric MDS identified a new class of predisposition genes (SAMD9 and SAMD9L) in nearly 20% of children with MDS.   These children universally also have somatic loss of chromosome 7 (monosomy 7), which can further drive disease progression.  These findings have made an immediate impact on patient care, including both diagnosis and monitoring. We have likewise identified somatic enhancer hijacking events involving the transcription factor MECOM as a driving event in pediatric therapy-related myeloid neoplasms.  Currently we are identifying the genetic alterations that drive relapsed pediatric AML.  

Klco Lab

Associations between cytogenetic abnormalities and recurrent mutations in myeloid neoplasms. [Schwartz et al, Nature Communication 2017]

Modeling and functional genomics of pediatric MDS/AML

We are using a wide range of sequencing and genetic engineering approaches to interrogate the role of recurrent and newly identified genetic alterations in the pathogenesis of pediatric myeloid tumors and to identify potential therapeutic vulnerabilities.  Current projects leverage human model systems (primary cord blood CD34-positive cells), CRISPR-Cas9 technology, and in vivo mouse models (patient derived xenografts and genetically engineered mouse models) to create representative models that can be used to decipher the mechanisms of disease development, progression and for the establishment of pre-clinical models of MDS/AML to support therapeutic development. Notably, we have developed a series of human and mouse systems to model the impact of germline mutations in SAMD9 and SAMD9L on hematopoietic cell function and fitness.  In addition, we have established a number of collaborations at St Jude and beyond to decipher the molecular consequences of NUP98 fusion oncoprotein expression and to investigate the potential role of protein degradation approaches to target critical transcription factors in pediatric tumors.  

Klco Lab

Evolution of myeloid tumors

Our laboratory is interested in deciphering the clonal architecture and progression of myeloid tumors from diagnosis to relapse in response to different chemotherapeutic pressures. Single cell technologies, deep sequencing and cell free DNA testing help to define the spectrum of genetic mutations in pediatric tumors and how the change over time as a result of chemotherapy. This approach not only aids in our understanding of the tumor response at a granular level, but facilitates the establishment of new benchmarks for minimal residual disease testing. Much of this work is in collaboration with Dr. Xiaotu Ma at St Jude.

Klco Lab

Selected Publications

Contact us

Jeffery M. Klco, MD, PhD

MS342, Room D4047B
St. Jude Children’s Research Hospital

262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
901-595-6807 Jeffery.Klco@stjude.org

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262 Danny Thomas Place
Memphis, TN, 38105-3678 USA