Near-Haploidy and Low-Hypodiploidy in B-Cell Acute Lymphoblastic Leukemia : When Less Is Too Much
Molina, Oscar (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Bataller, Alex (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Thampi, Namitha (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ribera Salas, Jordi (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Granada, Isabel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Velasco, Pablo (Hospital Universitari Vall d'Hebron)
Fuster, José Luis (Spanish Network for Advanced Therapies RICORS-TERAV)
Menéndez Bujan, Pablo (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Fecha:	2021
Resumen:	B-cell acute lymphoblastic leukemia (B-ALL) is characterized by an uncontrolled proliferation of blood cells in the bone marrow. A small fraction of B-ALL patients shows abnormally low chromosome numbers, defined as hypodiploidy, in leukemic cells. Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-ALL and is associated to an extremely poor outcome, with low survival rates both in pediatric and adult cases. In this review, we describe the main clinical and genetic features of hypodiploid B-ALL subtypes with less than 40 chromosomes, the current treatment protocols and their clinical outcomes. Additionally, we discuss the potential cellular mechanisms involved on the origin of hypodiploidy, as well as its leukemogenic impact. Studies aiming to decipher the biological mechanisms involved in hypodiploid subtypes of B-ALL with less than 40 chromosomes are crucial to improve the poor survival rates in these patients. Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-cell acute lymphoblastic leukemia (B-ALL). This condition can be classified based on modal chromosome number as low-hypodiploidy (30-39 chromosomes) and near-haploidy (24-29 chromosomes), with unique cytogenetic and mutational landscapes. Hypodiploid B-ALL with <40 chromosomes has an extremely poor outcome, with 5-year overall survival rates below 50% and 20% in childhood and adult B-ALL, respectively. Accordingly, this genetic feature represents an adverse prognostic factor in B-ALL and is associated with early relapse and therapy refractoriness. Notably, half of all patients with hypodiploid B-ALL with <40 chromosomes cases ultimately exhibit chromosome doubling of the hypodiploid clone, resulting in clones with 50-78 chromosomes. Doubled clones are often the major clones at diagnosis, leading to "masked hypodiploidy", which is clinically challenging as patients can be erroneously classified as hyperdiploid B-ALL. Here, we summarize the main cytogenetic and molecular features of hypodiploid B-ALL subtypes, and provide a brief overview of the diagnostic methods, standard-of-care treatments and overall clinical outcome. Finally, we discuss molecular mechanisms that may underlie the origin and leukemogenic impact of hypodiploidy and may open new therapeutic avenues to improve survival rates in these patients.
Ayudas:	Agencia Estatal de Investigación PID2019-108160RB-I00 European Commission 646903 European Commission 811220
Nota:	Altres ajuts: Asociación Española Contra el Cáncer, INVES211226MOLI
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Hypodiploidy ; Near-haploidy ; B-cell acute lymphoblastic leukemia ; Clinical biomarkers ; Patient stratification
Publicado en:	Cancers, Vol. 14 (2021) , ISSN 2072-6694

DOI: 10.3390/cancers14010032
PMID: 35008193

21 p, 1.7 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
Artículos > Artículos de investigación
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