RT Journal Article
T1 Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid
A1 Sanchez, Ricardo
A1 Ayala, Rosa
A1 Alonso, Rafael Alberto
A1 Martínez, María Pilar
A1 Ribera, Jordi
A1 García, Olga
A1 Sanchez-Pina, José
A1 Mercadal, Santiago
A1 Montesinos, Pau
A1 Martino, Rodrigo
A1 Barba, Pere
A1 González-Campos, José
A1 Barrios, Manuel
A1 Lavilla, Esperanza
A1 Gil, Cristina
A1 Bernal, Teresa
A1 Escoda, Lourdes
A1 Abella, Eugenia
A1 Amigo, Ma Luz
A1 Moreno, Ma José
A1 Bravo, Pilar
A1 Guàrdia, Ramón
A1 Hernández-Rivas, Jesús-María
A1 García-Guiñón, Antoni
A1 Piernas, Sonia
A1 Ribera, José-María
A1 Martínez-López, Joaquín
K1 Neoplasia
K1 Acute lymphoblastic leukemia relapse
K1 Central nervous system
K1 Mutation analysis
K1 Humanos
K1 Mesilato de imatinib
K1 Mutación
K1 Leucemia-Linfoma linfoblástico de células precursoras
K1 Proteínas proto-oncogénicas c-bcr
K1 Recurrencia
K1 Médula ósea
K1 Evolución clonal
K1 ADN complementario
K1 Secuenciación de nucleótidos de alto rendimiento
K1 BCR-ABL1
AB We investigated the frequency, predictors, and evolution of acute lymphoblastic leukemia (ALL) in patients with CNS relapse and introduced a novel method for studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analyzed in two PETHEMA clinical trials. All achieved complete remission after imatinib treatment. Of these, 30 (23%) experienced a relapse after achieving complete remission, and 13 (10%) had an isolated CNS relapse or combined CNS and BM relapses. We compared the characteristics of patients with and without CNS relapse and further analyzed CSF and BM samples from two of the 13 patients with CNS relapse. In both patients, classical sequencing analysis of the kinase domain of BCR-ABL1 from the cDNA of CSF blasts revealed the pathogenic variant p.L387M. We also performed ultra-deep next-generation sequencing (NGS) in three samples from one of the relapsed patients. We did not find the mutation in the BM sample, but we did find it in CSF blasts with 45% of reads at the time of relapse. These data demonstrate the feasibility of detecting BCR-ABL1 mutations in CSF blasts by NGS and highlight the importance of monitoring clonal evolution over time.
PB Springer Verlag
SN 0939-5555
YR 2017
FD 2017-04-27
LK http://hdl.handle.net/10668/2672
UL http://hdl.handle.net/10668/2672
LA en
NO Sanchez R, Ayala R, Alonso RA, Marínez MP, Ribera J, García O, et al. Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid. Ann Hematol. 2017 Apr 27.
NO This work was supported by the Fundación CRIS and Red Temática de Investigación Cooperativa en Cáncer (RTICC),Instituto de Salud Carlos III (Ref.: RD12/0036/0061).
DS RISalud
RD Apr 10, 2025