Therapy‐related myeloid neoplasms resembling juvenile myelomonocytic leukemia: a case series and review of the literature

2021 ◽  
Author(s):  
Astrid Wintering ◽  
Stephen Smith ◽  
Beng Fuh ◽  
Arun Rangaswami ◽  
Gary Dahl ◽  
...  
Keyword(s):  
Case Series ◽  
Juvenile Myelomonocytic Leukemia ◽  
Review Of The Literature ◽  
Myeloid Neoplasms ◽  
Myelomonocytic Leukemia

Juvenile myelomonocytic leukemia: A case series of a rare hematological disease

2020 ◽  
Vol 57 (1) ◽  
pp. 105
Author(s):  
SreeRekha Jinkala ◽  
KalaivaniS Subramanian ◽  
Rakhee Kar ◽  
Debdatta Basu ◽  
Biswajit Dubashi
Keyword(s):  
Case Series ◽  
Juvenile Myelomonocytic Leukemia ◽  
Hematological Disease ◽  
Myelomonocytic Leukemia

scholarly journals Deficiency of Cux1, Encoded on Human Chromosome 7q, Causes Aberrant Hematopoietic Stem Cell Function and Spontaneous Myeloproliferative Disease in Mice

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 789-789
Author(s):  
Ningfei An ◽  
Saira Khan ◽  
Molly Imgruet ◽  
Sandeep Gurbuxani ◽  
Michael R. Burgess ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
Juvenile Myelomonocytic Leukemia ◽  
Normocytic Anemia ◽  
Hematopoietic Stem ◽  
Altered Expression ◽  
Myeloid Malignancies ◽  
Myeloid Neoplasms ◽  
Myelomonocytic Leukemia

Abstract Loss of all or part of chromosome 7 [-7/del(7q)] is a common, high-risk cytogenetic abnormality identified in a variety myeloid malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia, therapy-related myeloid neoplasms, juvenile myelomonocytic leukemia (JMML) and chronic myelomonocytic leukemia (CMML). CUX1 is a non-clustered, homeodomain-containing transcription factor encoded on the commonly deleted region of 7q22. CUX1 inactivating mutations occur across solid tumors and myeloid neoplasms, and carry a poor prognosis in myeloid malignancies independently of 7q status. Previously, we reported that CUX1 is a conserved, haploinsufficient, myeloid tumor suppressor. To determine the mechanism by which CUX1 regulates leukemogenesis, we generated an inducible, shRNA-transgenic, Cux1 -knockdown mouse model. Insufficient Cux1 levels caused early mortality in mice, due to a spontaneous myeloproliferative disorder with features of CMML/JMML and MDS. Cux1 deficient mice had a significant increase in myelomonocytic cell numbers in the peripheral blood, bone marrow, and spleen. Cux1 deficiency led to extramedullary hematopoiesis, splenomegaly, and an increase in megakaryocyte numbers and megakaryocyte dysplasia. In addition, Cux1 is required for normal red cell development, as Cux1 knockdown led to a normocytic anemia due to an erythroblast maturation arrest. To identify CUX1 transcriptional targets, we performed gene expression profiling after CUX1 knockdown in CD34+ human hematopoietic stem and progenitor cells (HSPCs). Differentially expressed genes were enriched for genes deregulated in JMML and -7/del(7q) MDS, in addition to altered expression of quiescent, proliferative, and myeloid differentiation pathways. Consistent with these gene signatures, Cux1 maintains hematopoietic stem cell quiescence and represses HSPC proliferation, self-renewal, and granulocyte/monocyte differentiation. Thus Cux1 has pleotropic roles in multiple myeloid lineages. Deletion of CUX1, in the context of -7/del(7q), may facilitate myeloid transformation through aberrant transcriptional regulation of HSPC differentiation and proliferation. Disclosures No relevant conflicts of interest to declare.

CBL Mutations In Therapy-Related Leukemia and Infant Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2149-2149
Author(s):  
Norio Shiba ◽  
Tomohiko Taki ◽  
Myoung-ja Park ◽  
Masayuki Nagasawa ◽  
Jyunko Takita ◽  
...  
Keyword(s):  
Gene Rearrangement ◽  
Ring Finger ◽  
Gene Mutations ◽  
Juvenile Myelomonocytic Leukemia ◽  
Ring Finger Domain ◽  
Mll Gene ◽  
Myeloid Neoplasms ◽  
Myelomonocytic Leukemia ◽  
Mll Gene Rearrangement ◽  
Infant Leukemia

Abstract Abstract 2149 Recent reports of somatic mutations of the CBL proto-oncogene in myeloid neoplasms are intriguing, because these CBL mutations were shown to results in aberrant tyrosine kinase signaling, which would lead also to activation of RAS signaling pathways. We and others reported that CBL mutations occurred in a variety of myeloid neoplasms, including de novo acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and MDS/myeloproliferative neoplasm, especially in chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML). The importance of CBL mutations concerning leukemogenesis is substantially increased. We investigated CBL mutations in 20 therapy-related leukemia/MDS (t-Leuk/MDS) cases and 26 infant leukemia cases. Homozygous mutation of theCBL gene (P417R), which was located in the RING finger domain, was identified in one out of 20 (5%) t-Leuk/MDS cases. This patient was a 5 year-old boy, whose biopsied specimen of the buccal lymph node showed malignant lymphoma (diffuse large T cell type, MT1(+), MB1(-), UCHL1(+)). No pathogenic nucleotide changes were identified in the CBL gene in the initial sample. Subsequently, the patient was treated with chemotherapy including VP-16 (200 mg/m2) given twice weekly. Nineteen months after initial diagnosis, he was diagnosed as having therapy-related leukemia with t(5;21) and MLL gene rearrangement due to VP-16. Furthermore, CBL gene mutations were found in 3 of 26 (12%) infant leukemia cases with 11q23 translocation/MLL gene rearrangement. CBL gene mutations were located in splice site in intron 8 and the RING finger domain (Y371H, in 2 cases), SNP array analysis (Affymetrix, GeneChip) of these cases with mutated CBL gene disclosed 11q-acquired uniparental disomy in all cases, but not in cases with wild-type CBL. CBL mutation has not been reported in acute leukemia with 11q23 translocation/MLL gene rearrangement. To our knowledge, these are the first t-Leuk/MDS case and infant cases with 11q23 translocation/MLL rearrangement, suggesting that CBL is mutated in a unique subset of t-Leuk/MDS and infant leukemia which is considered to play a pathogenic role in the development of t-Leuk/MDS and infant leukemia. Further accumulation of cases with t-Leuk/MDS and infant leukemia having the CBL mutation is needed. Disclosures: No relevant conflicts of interest to declare.

Prognostic relevance of disordered epigenetic regulation in juvenile myelomonocytic leukemia

2013 ◽  
Vol 225 (03) ◽  
Author(s):  
S Fluhr ◽  
T Witte ◽  
CF Krombholz ◽  
C Plass ◽  
CM Niemeyer ◽  
...  
Keyword(s):  
Epigenetic Regulation ◽  
Juvenile Myelomonocytic Leukemia ◽  
Prognostic Relevance ◽  
Myelomonocytic Leukemia

Immunosuppression as efficient therapy for Eosinophilic cholangitis: A case series and review of the literature

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
D Reher ◽  
C Schramm ◽  
F Brinkert ◽  
A Lohse ◽  
C Weiler-Normann
Keyword(s):  
Case Series ◽  
Review Of The Literature ◽  
Eosinophilic Cholangitis

Two Cases of Juvenile Dermatomyositis: Case Series and Review of the Literature

2019 ◽  
Vol 81 (1) ◽  
pp. 14-17
Author(s):  
Yuka KUNIMI ◽  
Yasunori OHGA ◽  
Kotaro ITO ◽  
Shinichi HIROSE ◽  
Shinichi IMAFUKU
Keyword(s):  
Juvenile Dermatomyositis ◽  
Case Series ◽  
Review Of The Literature
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