Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice‐site mutations: Two case reports and a literature review

Castro, Inês Rugani Ribeiro de; Galán-Gómez, Víctor; Corral-Sánchez, María Dolores; Pérez‐Martínez, Antonio; Riesco, Susana; Isidoro‐García, María

doi:10.1002/ccr3.4260

Cited by 5 publications

(11 citation statements)

References 26 publications

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“…CBL mutations have to be included in the differential diagnosis of foetal pleural effusions, hydrops fetalis, and foetal nuchal oedema [ 76 ]. There is a significantly increased risk of JMML development [ 79 ].…”

Section: Syndromes Predisposing To Haematological Malignanciesmentioning

confidence: 99%

Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies—A Review

Filipiuk

Kozakiewicz

Kośmider

et al. 2022

Cancers

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The view of paediatric cancer as a genetic disease arises as genetic research develops. Germline mutations in cancer predisposition genes have been identified in about 10% of children. Paediatric cancers are characterized by heterogeneity in the types of genetic alterations that drive tumourigenesis. Interactions between germline and somatic mutations are a key determinant of cancer development. In 40% of patients, the family history does not predict the presence of inherited cancer predisposition syndromes and many cases go undetected. Paediatricians should be aware of specific symptoms, which highlight the need of evaluation for cancer syndromes. The quickest possible identification of such syndromes is of key importance, due to the possibility of early detection of neoplasms, followed by presymptomatic genetic testing of relatives, implementation of appropriate clinical procedures (e.g., avoiding radiotherapy), prophylactic surgical resection of organs at risk, or searching for donors of hematopoietic stem cells. Targetable driver mutations and corresponding signalling pathways provide a novel precision medicine strategy.Therefore, there is a need for multi-disciplinary cooperation between a paediatrician, an oncologist, a geneticist, and a psychologist during the surveillance of families with an increased cancer risk. This review aimed to emphasize the role of cancer-predisposition gene diagnostics in the genetic surveillance and medical care in paediatric oncology.

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Section: Syndromes Predisposing To Haematological Malignanciesmentioning

confidence: 99%

Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies—A Review

Filipiuk

Kozakiewicz

Kośmider

et al. 2022

Cancers

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“…The percentage of germline CBL mutations detected in JMML patients varies up to 17% in the largest studies [26,[46][47][48][49]. Most of these patients show constitutional anomalies consistent with CBL syndrome, which include Noonanlike features (developmental delay, congenital heart defects, and craniofacial anomalies), neurologic deficits, and pigmented skin lesions [34,48,50,51]. CBL syndrome carries an increased risk for JMML.…”

Section: Rasopathiesmentioning

confidence: 99%

“…CBL syndrome carries an increased risk for JMML. Whereas the few recently described cases of JMML with a somatic CBL mutations were refractory to chemotherapy [ 34 ], the clinical course of JMML with a germline CBL mutation is heterogeneous with some cases showing spontaneous regression and others behaving aggressively [ 34 , 50 , 51 ].…”

Section: Juvenile Myelomonocytic Leukemia and Related Diseasesmentioning

confidence: 99%

EAHP 2020 workshop proceedings, pediatric myeloid neoplasms

et al. 2022

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The first section of the bone marrow workshop of the European Association of Haematopathology 2020 Virtual Meeting was dedicated to pediatric myeloid neoplasms. The section covered the whole spectrum of myeloid neoplasms, including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), and acute myeloid leukemia. The workshop cases are hereby presented, preceded by an introduction on these overall rare diseases in this age group. Very rare entities such as primary myelofibrosis, pediatric MDS with fibrosis, and MDS/MPN with JMML-like features and t(4;17)(q12;q21); FIP1L1::RARA fusion, are described in more detail.

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“…Although the phenotype of children affected by CBL syndrome has been increasingly delineated over time ( 4 , 5 ), the immunological features of CBL syndrome have not been extensively described. Here we describe two patients with identical germline CBL mutation [c.1259G > A; (pR420Q)], expanding the immunological phenotypic spectrum of RASopathies and CBL syndrome.…”

Section: Introductionmentioning

confidence: 99%

“…Confirming the variant in hair follicles or fibroblasts is crucial in order to prove the germline origin of the genetic lesion and distinguishing Noonan-like syndromes from RALD. To date, more than 50 cases of CBL syndrome have been reported and the majority of them developed JMML ( 4 ). JMML is a myeloproliferative/myelodysplastic neoplasm of early childhood characterized by rapidly progressive disease requiring allogeneic hematopoietic stem cell transplantation as potentially curative treatment in the majority of the patients.…”

Section: Introductionmentioning

confidence: 99%

Abnormal B-Cell Maturation and Increased Transitional B Cells in CBL Syndrome

et al. 2022

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CBL syndrome is a Noonan-like RASopathy with heterogeneous clinical phenotype and predisposition to juvenile myelomonocytic leukemia (JMML). Here we describe two patients with identical germline CBL mutation and clinical and immune-hematological overlapping features with autoimmune lymphoproliferative syndrome (ALPS) and B-cell expansion with NF-κB and T-cell anergy (BENTA) syndrome. Increased immature/transitional B cells can be depicted in CBL syndrome, ALPS, and BENTA. Nonetheless, our patients here described showed peculiar B-cell phenotype due to increased immature/transitional CD34+ B cells. This feature differentiates CBL syndrome from BENTA, pointing toward an abnormal proliferation of B-cell early precursors.

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Juvenile myelomonocytic leukemia in CBL syndrome associated with germline splice‐site mutations: Two case reports and a literature review

Abstract: This is an open access article under the terms of the Creative Commons Attribution NonCommercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non commercial and no modifications or adaptations are made.

Cited by 5 publications

References 26 publications

Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies—A Review

Genetic Disorders with Predisposition to Paediatric Haematopoietic Malignancies—A Review

EAHP 2020 workshop proceedings, pediatric myeloid neoplasms

Abnormal B-Cell Maturation and Increased Transitional B Cells in CBL Syndrome

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