Introduction: Relapse of acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic cell transplantation (HCT) is a therapeutic challenge. We present the case of a 20-year-old patient with a relapse of Philadelphia chromosome-negative ALL B-common over 2 years after HCT with no response to salvage chemotherapy or blinatumomab, who finally responded to a molecularly tailored therapy adjusted to the BCR-ABL1-like phenotype.
Methods: The BCR-ABL1-like phenotype was diagnosed on the basis of an increased expression of ABL1 and CRLF2 genes.
Results: We combined a nilotinib-based therapy targeting the overexpressed ABL1 gene with a proteasome inhibitor and Peg-asparaginase, achieving a spectacular response: the percentage of lymphoblasts in the bone marrow was reduced from 70% to 5%, which enabled a second HCT to be performed. Moreover, the relatively low toxicity of the treatment led to a good quality of life and no need for prolonged hospitalization.
Conclusion: To our knowledge, this is the first successful use of nilotinib in BCR-ABL1-like phenotype ALL. This case should encourage routine clinical use of molecular data to individualize therapies targeting the overexpressed pathways responsible for leukemic cell proliferation, as a means to overcome chemoresistance.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1159/000490121 | DOI Listing |
Pediatr Blood Cancer
March 2025
Departments of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Rearrangements of cytokine receptor-like factor 2 gene (CRLF2) are present in ∼50% of B-lymphoblastic leukemia/lymphoma (B-ALL) with BCR::ABL1-like features. Herein, we report three patients with CRLF2-rearranged mixed phenotype acute leukemia (MPAL). All three cases were B/myeloid MPAL in young patients harboring P2RY8::CRLF2 or IGH::CRLF2 with additional genomic alterations in signaling (JAK and RAS) and cell cycle (CDKN2A/B) pathways, a genomic profile similar to that in BCR::ABL1-like B-ALL.
View Article and Find Full Text PDFArch Pathol Lab Med
February 2025
From the Department of Medical and Molecular Genetics (Booth, Smith, Stohler, Vance), Center for Computational Biology and Bioinformatics, Department of Medical and Molecular Genetics (Gao, Liu), and the Department of Pathology and Laboratory Medicine (Vance), Indiana University School of Medicine, Indianapolis.
Context.—: Pediatric B-cell acute lymphoblastic leukemia is genetically and phenotypically heterogeneous, with a genetic landscape including chromosomal translocations that disrupt ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1).
Objective.
Introduction: Relapse of acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic cell transplantation (HCT) is a therapeutic challenge. We present the case of a 20-year-old patient with a relapse of Philadelphia chromosome-negative ALL B-common over 2 years after HCT with no response to salvage chemotherapy or blinatumomab, who finally responded to a molecularly tailored therapy adjusted to the BCR-ABL1-like phenotype.
Methods: The BCR-ABL1-like phenotype was diagnosed on the basis of an increased expression of ABL1 and CRLF2 genes.
Haematologica
September 2016
CLIP, Department of Pediatric Hematology and Oncology, 2 Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
To characterize the incidence, clinical features and genetics of ETV6-ABL1 leukemias, representing targetable kinase-activating lesions, we analyzed 44 new and published cases of ETV6-ABL1-positive hematologic malignancies [22 cases of acute lymphoblastic leukemia (13 children, 9 adults) and 22 myeloid malignancies (18 myeloproliferative neoplasms, 4 acute myeloid leukemias)]. The presence of the ETV6-ABL1 fusion was ascertained by cytogenetics, fluorescence in-situ hybridization, reverse transcriptase-polymerase chain reaction and RNA sequencing. Genomic and gene expression profiling was performed by single nucleotide polymorphism and expression arrays.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!