Relapse of precursor B-cell acute lymphoblastic leukemia as an isolated central nervous system mass lesion 9 years after initial diagnosis

Lowichik, Amy; Bernini, Juan Carlos; Tonk, V.; Ansari, M. Qasim; Rollins, Nancy; Winick, N. J.; Timmons, Charles F.

doi:10.1002/(sici)1096-911x(199602)26:2<129::aid-mpo11>3.0.co;2-d

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…We found that meningeal spaces harbored BCP‐ALL blasts after a week of engraftment. Massive infiltration and colonization at brain parenchyma was not observed until late stages of engraftment approaching end‐stage disease, consistent with the relative rarity of intracerebral metastases reported in human patients . These events were associated with reduced integrity of the BBB and activation of endothelial cells and astrocytes in the brain.…”

Section: Introductionsupporting

confidence: 77%

“…The NALM6 model may be particularly useful for understanding processes that lead to leukemia invasion of brain parenchyma, which was associated with only 10% of cases in a 1972 study of 126 autopsies . Case reports of intracerebral metastases remain relatively rare; because these cases were all associated with relapse, it is possible that occasional intraparenchymal colonies can offer leukemia cells sanctuary from standard treatments. The resolution of current brain imaging capabilities in the clinic is likely to be too low to capture small lesions, providing some explanation for relapse of specific individuals that cannot be predicted from routine CSF sampling with the administration of intrathecal therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Massive infiltration and colonization at brain parenchyma was not observed until late stages of engraftment approaching end-stage disease, consistent with the relative rarity of intracerebral metastases reported in human patients. [32][33][34][35][36][37][38] These events were associated with reduced integrity of the BBB and activation of endothelial cells and astrocytes in the brain. We report that brain endothelial cells and astrocytes can be modulated by exosomes released from leukemia blasts and upregulate VEGF-A for sequential BBB disruption with leukemia CNS invasion.…”

Section: Introductionmentioning

confidence: 99%

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Leukemia-derived exosomes and cytokines pave the way for entry into the brain

Kinjyo

Bragin²,

Grattan

et al. 2019

Journal of Leukocyte Biology

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Infiltration of acute lymphoblastic leukemia (ALL) blasts into the CNS remains as a major clinical problem, with high risk for chemotherapy‐resistant relapse and treatment‐related morbidity. Despite the common inclusion of CNS prophylaxis treatments in therapy regimens, there are significant gaps in understanding the mechanisms that mediate leukemia cell entry into the CNS as well as roles for resident cells in the brain. In this study, we employ a xenograft model of human B cell precursor (BCP)‐ALL in immunocompromised mice. This model system recapitulates key pathological characteristics of leptomeningeal involvement seen in patients and provides insights into rare cases that involve parenchymal invasion. We examine the infiltration of engrafted leukemia blasts into brains of recipient mice and provide evidence that the interaction between blasts and brain resident cells causes aberrant activation of host cells in the brain microenvironment. BCP‐ALL blasts also release multiple cytokines and exosomes containing IL‐15 that bind and are internalized by astrocytes and brain vessel endothelial cells. Leukemic invasion is linked to production of VEGF‐AA by astrocytes and disruption of the blood‐brain‐barrier (BBB) integrity. Knockdown of either IL‐15 or IL‐15Rα in the NALM6 cell line decreases CNS infiltration in engrafted mice. These results provide important insights into the multiple mechanisms by which lymphoblasts modulate the brain microenvironment to breach the BBB for metastatic invasion.

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Section: Introductionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Leukemia-derived exosomes and cytokines pave the way for entry into the brain

Kinjyo

Bragin²,

Grattan

et al. 2019

Journal of Leukocyte Biology

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“…11 To our knowledge, there have been only 8 biopsyproven case reports of intracranial mass lesions in patients with ALL that were caused by the original leukemia. 8,[12][13][14][15][16][17][18] These case reports refer to focal intracranial collections of ALL cells by a variety of terms, including myeloid sarcomas, granulocytic sarcomas, and chloromas. These terms are inaccurate and should be reserved for focal collections of leukemic cells of myeloid origin that express the enzyme myeloperoxidase.…”

Section: Discussionmentioning

confidence: 99%

A Man in His 40s With Headache, Lethargy, and Altered Mental Status

et al. 2015

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A right-handed man in his 40s with no significant medical history presented with 1 month of fatigue, confusion, and headache. He initially had increased sleep requirements accompanied by poor work performance that progressed to obtundation. Associated with these symptoms, he reported several weeks of night sweats and a 10-lb unintentional weight loss. He denied any history of recent trauma or head injury. Findings from the general examination revealed leftsided cervical adenopathy and splenomegaly. Findings from the neurologic examination demonstrated markedly diminished arousal but normal cranial nerve function, motor strength, and reflexes.

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“…B-cell acute lymphoblastic leukemia (B-ALL) is a type of ALL caused by malignant transformation and cloning of B-cell precursors in the bone marrow and thymus (1)(2)(3). Patients with B-ALL usually present with symptoms such as infection, anemia, hemorrhage, and tissue infiltration, which arise owing to the destruction of normal hematopoietic function and the accumulation of tumor cells (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Treatment for a B-cell acute lymphoblastic leukemia patient carrying a rare TP53 c.C275T mutation: A case report

Wang

et al. 2023

Front. Oncol.

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TP53 mutations are associated with poor prognosis in the vast majority of cancers. In this study, we present a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient carrying a rare TP53 c.C275T mutation. This extremely rare mutation affects an amino acid residue located between the TAD domain and the DNA-binding domain of p53. The patient was resistant to most conventional chemotherapy regimens and remained minimal residual disease (MRD)-positive after five rounds of such regimens. We tested the sensitivity of the patient’s leukemic cells to 21 anti-cancer drugs by performing in vitro drug sensitivity assays. The results showed that bortezomib had a very strong killing effect on the patient’s leukemic cells. Therefore, we subsequently treated the patient with bortezomib combined with vindesine, cytarabine, and fludarabine. After one course of treatment, the patient became MRD-negative, and there was no recurrence during a 9-month follow-up. In conclusion, our report suggests that the TP53 c.C275T mutation is associated with poor prognosis in B-ALL. Fortunately, bortezomib combined with chemotherapy could achieve a better therapeutic effect than conventional regimens in this type of ALL.

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Relapse of precursor B-cell acute lymphoblastic leukemia as an isolated central nervous system mass lesion 9 years after initial diagnosis

Cited by 7 publications

References 34 publications

Leukemia-derived exosomes and cytokines pave the way for entry into the brain

Leukemia-derived exosomes and cytokines pave the way for entry into the brain

A Man in His 40s With Headache, Lethargy, and Altered Mental Status

Treatment for a B-cell acute lymphoblastic leukemia patient carrying a rare TP53 c.C275T mutation: A case report

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