Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1
Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature ste...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2013/349067 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832557012781629440 |
|---|---|
| author | Jessica Purizaca Adriana Contreras-Quiroz Elisa Dorantes-Acosta Eduardo Vadillo Lourdes Arriaga-Pizano Silvestre Fuentes-Figueroa Horacio Villagomez-Barragán Patricia Flores-Guzmán Antonio Alvarado-Moreno Hector Mayani Isaura Meza Rosaura Hernandez Sara Huerta-Yepez Rosana Pelayo |
| author_facet | Jessica Purizaca Adriana Contreras-Quiroz Elisa Dorantes-Acosta Eduardo Vadillo Lourdes Arriaga-Pizano Silvestre Fuentes-Figueroa Horacio Villagomez-Barragán Patricia Flores-Guzmán Antonio Alvarado-Moreno Hector Mayani Isaura Meza Rosaura Hernandez Sara Huerta-Yepez Rosana Pelayo |
| author_sort | Jessica Purizaca |
| collection | DOAJ |
| description | Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested. |
| format | Article |
| id | doaj-art-404d396db644438d871b75dce495a2db |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-404d396db644438d871b75dce495a2db2025-02-03T05:43:50ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/349067349067Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1Jessica Purizaca0Adriana Contreras-Quiroz1Elisa Dorantes-Acosta2Eduardo Vadillo3Lourdes Arriaga-Pizano4Silvestre Fuentes-Figueroa5Horacio Villagomez-Barragán6Patricia Flores-Guzmán7Antonio Alvarado-Moreno8Hector Mayani9Isaura Meza10Rosaura Hernandez11Sara Huerta-Yepez12Rosana Pelayo13Oncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, MexicoOncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, Mexico“Federico Gómez” Children’s Hospital, 06720 Mexico City, DF, MexicoOncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, MexicoImmunochemistry Research Unit, Medical Specialties Hospital, Mexican Institute for Social Security, 06720 Mexico City, DF, MexicoUMAE “Victorio de la Fuente Narváez”, Mexican Institute for Social Security, 07760 Mexico City, DF, MexicoUMAE “Victorio de la Fuente Narváez”, Mexican Institute for Social Security, 07760 Mexico City, DF, MexicoOncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, Mexico“Carlos McGregor Sanchez” Hospital, Mexican Institute for Social Security, 03100 Mexico City, DF, MexicoOncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, MexicoMolecular Biomedicine Program, CINVESTAV, 07360 Mexico City, DF, MexicoMolecular Biomedicine Program, CINVESTAV, 07360 Mexico City, DF, Mexico“Federico Gómez” Children’s Hospital, 06720 Mexico City, DF, MexicoOncology Research Unit, Oncology Hospital, Mexican Institute for Social Security, Avenue Cuauhtemoc 330, Colonia Doctores, 06720 Mexico City, DF, MexicoAcute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.http://dx.doi.org/10.1155/2013/349067 |
| spellingShingle | Jessica Purizaca Adriana Contreras-Quiroz Elisa Dorantes-Acosta Eduardo Vadillo Lourdes Arriaga-Pizano Silvestre Fuentes-Figueroa Horacio Villagomez-Barragán Patricia Flores-Guzmán Antonio Alvarado-Moreno Hector Mayani Isaura Meza Rosaura Hernandez Sara Huerta-Yepez Rosana Pelayo Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1 Clinical and Developmental Immunology |
| title | Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1 |
| title_full | Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1 |
| title_fullStr | Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1 |
| title_full_unstemmed | Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1 |
| title_short | Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1 |
| title_sort | lymphoid progenitor cells from childhood acute lymphoblastic leukemia are functionally deficient and express high levels of the transcriptional repressor gfi 1 |
| url | http://dx.doi.org/10.1155/2013/349067 |
| work_keys_str_mv | AT jessicapurizaca lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT adrianacontrerasquiroz lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT elisadorantesacosta lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT eduardovadillo lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT lourdesarriagapizano lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT silvestrefuentesfigueroa lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT horaciovillagomezbarragan lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT patriciafloresguzman lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT antonioalvaradomoreno lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT hectormayani lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT isaurameza lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT rosaurahernandez lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT sarahuertayepez lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 AT rosanapelayo lymphoidprogenitorcellsfromchildhoodacutelymphoblasticleukemiaarefunctionallydeficientandexpresshighlevelsofthetranscriptionalrepressorgfi1 |