Elory Leonard | Karolinska Institutet (original) (raw)

Papers by Elory Leonard

Research paper thumbnail of Skin mesenchymal niches maintain and protect AML-initiating stem cells

Journal of Experimental Medicine, Jul 26, 2023

Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifest... more Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in the skin in a transplantation-induced MLL-AF9 AML mouse model. These AML cells could regenerate AML after transplantation. Prospective niche characterization revealed that skin harbored mesenchymal progenitor cells (MPCs) with a similar phenotype as BM mesenchymal stem cells. These skin MPCs protected AML-initiating stem cells (LSCs) from chemotherapy in vitro partially via mitochondrial transfer. Furthermore, Lama4 deletion in skin MPCs promoted AML LSC proliferation and chemoresistance. Importantly, more chemoresistant AML LSCs appeared to be retained in Lama4−/− mouse skin after cytarabine treatment. Our study reveals the characteristics and previously unrecognized roles of skin mesenchymal niches in maintaining and protecting AML LSCs during chemotherapy, meriting future exploration of their impact on AML relapse.

Research paper thumbnail of Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option

Blood

Although tyrosine kinase inhibitors are effective for treating chronic myeloid leukemia (CML), th... more Although tyrosine kinase inhibitors are effective for treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be due to bone marrow (BM) niche protection. However, little is known about the underlying mechanisms. We here molecularly and functionally characterized BM niches in CML patients at diagnosis and revealed the altered niche composition and function in the CML patients. Long-term culture initiating cell (LTC-IC) assay showed that the mesenchymal stem cells from CML patients displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in CML patient BM cellular niches. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and ...

Research paper thumbnail of A Mesenchymal Cell Niche in Skin for Acute Myeloid Leukemia

Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifest... more Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in mouse skin. These cells were retained in the skin post-chemotherapy and could regenerate AML post-transplantation. The niche characterization revealed that skin harbored mesenchymal progenitor cells (MPCs) with a similar phenotype as BM mesenchymal stem cells. These skin MPCs maintained and protected AML-initiating stem cells (LSCs) from chemotherapy in vitro possibly via mitochondrial transfer. Furthermore, Lama4 deletion in skin MPCs promoted AML LSC proliferation and chemoresistance. Importantly, more chemoresistant AML LSCs were retained in Lama4−/- mouse skin post-cytarabine treatment. Our study reveals the characteristics and previously unrecognized roles of skin mesenchymal niches in maintaining AML...

Research paper thumbnail of Prevalence and Distribution of Thalassemia Trait Screening

Journal of thee Medical Sciences (Berkala Ilmu Kedokteran), 2017

Thalassemia is an inherited disorder of autosomal recessive gene caused by decrease or absent pro... more Thalassemia is an inherited disorder of autosomal recessive gene caused by decrease or absent production of one or two type of globin chain. This disorder will affect the quality and quantity of blood production. In Indonesia, thalassemia is not concerned as urgency, although it lies in thalassemia belt area. Thalassemia is classified according to the particular globin chain which affected such as a-thalassemia and b-thalassemia. Besides thalassemia, there are variant hemoglobinopathy called HbE. The aim of this study was to assess the prevalence of thalassemia carriers among the volunteer of screening in Yogyakarta Special Region from 2012 until 2015. The thalassemia carrier screening was conducted by collaborating with Indonesian Association of Parents of Children with Thalassemia (APCT) Yogyakarta. The hematological measurement and High-Performance Liquid Chromatography (HPLC) were performed on Prodia Laboratory Yogyakarta. The analysis of carriers prevalence was conducted in Laboratory of Genetics and Breeding, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta. Among 241 volunteers, we found 44 volunteers was diagnosed as b-thalassemia carrier, 30 volunteers as a-thalassemia carrier as well as HbE disorder carrier, and 1 volunteer was diagnosed as a-b-thalassemia carrier. The number of thalassemia carrier shows no significant difference each year. The prevalence of thalassemia carrier is high, even though the distribution is limited by the location where the screening took place. Nailil Husna et al., Prevalence and distribution of thalassemia trait screening b-thalasemia dan HbE serta satu pembawa a-b-thalasemia. Jumlah pembawa thalasemia tidak menunjukkan perbedaan yang signifikan setiap tahunnya. Prevalensi pembawa thalasemia tinggi, meskipun distribusinya dibatasi oleh lokasi dimana skrining dilakukan.

Research paper thumbnail of Skin mesenchymal niches maintain and protect AML-initiating stem cells

Journal of Experimental Medicine, Jul 26, 2023

Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifest... more Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in the skin in a transplantation-induced MLL-AF9 AML mouse model. These AML cells could regenerate AML after transplantation. Prospective niche characterization revealed that skin harbored mesenchymal progenitor cells (MPCs) with a similar phenotype as BM mesenchymal stem cells. These skin MPCs protected AML-initiating stem cells (LSCs) from chemotherapy in vitro partially via mitochondrial transfer. Furthermore, Lama4 deletion in skin MPCs promoted AML LSC proliferation and chemoresistance. Importantly, more chemoresistant AML LSCs appeared to be retained in Lama4−/− mouse skin after cytarabine treatment. Our study reveals the characteristics and previously unrecognized roles of skin mesenchymal niches in maintaining and protecting AML LSCs during chemotherapy, meriting future exploration of their impact on AML relapse.

Research paper thumbnail of Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option

Blood

Although tyrosine kinase inhibitors are effective for treating chronic myeloid leukemia (CML), th... more Although tyrosine kinase inhibitors are effective for treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be due to bone marrow (BM) niche protection. However, little is known about the underlying mechanisms. We here molecularly and functionally characterized BM niches in CML patients at diagnosis and revealed the altered niche composition and function in the CML patients. Long-term culture initiating cell (LTC-IC) assay showed that the mesenchymal stem cells from CML patients displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in CML patient BM cellular niches. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and ...

Research paper thumbnail of A Mesenchymal Cell Niche in Skin for Acute Myeloid Leukemia

Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifest... more Leukemia cutis or leukemic cell infiltration in skin is one of the common extramedullary manifestations of acute myeloid leukemia (AML) and signifies a poorer prognosis. However, its pathogenesis and maintenance remain understudied. Here, we report massive AML cell infiltration in mouse skin. These cells were retained in the skin post-chemotherapy and could regenerate AML post-transplantation. The niche characterization revealed that skin harbored mesenchymal progenitor cells (MPCs) with a similar phenotype as BM mesenchymal stem cells. These skin MPCs maintained and protected AML-initiating stem cells (LSCs) from chemotherapy in vitro possibly via mitochondrial transfer. Furthermore, Lama4 deletion in skin MPCs promoted AML LSC proliferation and chemoresistance. Importantly, more chemoresistant AML LSCs were retained in Lama4−/- mouse skin post-cytarabine treatment. Our study reveals the characteristics and previously unrecognized roles of skin mesenchymal niches in maintaining AML...

Research paper thumbnail of Prevalence and Distribution of Thalassemia Trait Screening

Journal of thee Medical Sciences (Berkala Ilmu Kedokteran), 2017

Thalassemia is an inherited disorder of autosomal recessive gene caused by decrease or absent pro... more Thalassemia is an inherited disorder of autosomal recessive gene caused by decrease or absent production of one or two type of globin chain. This disorder will affect the quality and quantity of blood production. In Indonesia, thalassemia is not concerned as urgency, although it lies in thalassemia belt area. Thalassemia is classified according to the particular globin chain which affected such as a-thalassemia and b-thalassemia. Besides thalassemia, there are variant hemoglobinopathy called HbE. The aim of this study was to assess the prevalence of thalassemia carriers among the volunteer of screening in Yogyakarta Special Region from 2012 until 2015. The thalassemia carrier screening was conducted by collaborating with Indonesian Association of Parents of Children with Thalassemia (APCT) Yogyakarta. The hematological measurement and High-Performance Liquid Chromatography (HPLC) were performed on Prodia Laboratory Yogyakarta. The analysis of carriers prevalence was conducted in Laboratory of Genetics and Breeding, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta. Among 241 volunteers, we found 44 volunteers was diagnosed as b-thalassemia carrier, 30 volunteers as a-thalassemia carrier as well as HbE disorder carrier, and 1 volunteer was diagnosed as a-b-thalassemia carrier. The number of thalassemia carrier shows no significant difference each year. The prevalence of thalassemia carrier is high, even though the distribution is limited by the location where the screening took place. Nailil Husna et al., Prevalence and distribution of thalassemia trait screening b-thalasemia dan HbE serta satu pembawa a-b-thalasemia. Jumlah pembawa thalasemia tidak menunjukkan perbedaan yang signifikan setiap tahunnya. Prevalensi pembawa thalasemia tinggi, meskipun distribusinya dibatasi oleh lokasi dimana skrining dilakukan.