<i>MECOM</i> gene overexpression in pediatric patients with acute myeloid leukemia

Elsherif, Mariam; Hammad, Mahmoud; Hafez, Hanafy; Yassin, Dina; Ashraf, Mohamed; Yasser, Nouran; Lehmann, Leslie; Elhaddad, Alaa

doi:10.1080/0284186x.2022.2025611

Cited by 6 publications

(8 citation statements)

References 20 publications

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“…1 It is now thought that the RUNX1::MECOM fusion transcript contributes directly to leukemogenesis or leukemic transformation. [14][15][16] Although the BM examination post-induction showed morphological remission, the aspirate was hemodiluted. Additionally, patient did not achieve cytogenetic or molecular remission till date.…”

Section: Discussionmentioning

confidence: 99%

“…Recent WHO classification of myeloid neoplasm also recognized rearrangements involving MECOM as a new AML type with poor prognosis 1 . It is now thought that the RUNX1::MECOM fusion transcript contributes directly to leukemogenesis or leukemic transformation 14–16 …”

Section: Discussionmentioning

confidence: 99%

“… 1 It is now thought that the RUNX1::MECOM fusion transcript contributes directly to leukemogenesis or leukemic transformation. 14 , 15 , 16 …”

Section: Discussionmentioning

confidence: 99%

“…Several studies demonstrate that MECOM rearranged AML regardless of therapy has a poor prognosis with significantly lower overall survival, event‐free survival, and higher cumulative incidence of relapse. 14 , 15 , 16 BCR‐ABL1 rearranged cases are also reported to be associated with poor prognosis, and there is a need for aggressive treatment 17 for achieving optimal outcome. This will also hold true when both BCR::ABL1 and RUNX1::MECOM coexist.…”

Section: Discussionmentioning

confidence: 99%

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A rare presentation of BCR‐ABL1 and RUNX1‐MECOM rearrangement in a pediatric patient with acute myeloid leukemia

Alamri,

Alanazi,

AlRajeh

et al. 2024

Clinical Case Reports

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Key Clinical MessageIn a patient with de novo AML, co‐existing BCR::ABL1 p190 isoform and RUNX1::MECOM rearrangement is accompanied by a very poor prognosis including limited response to treatment and no molecular remission. It is essential to develop a consensus on the therapeutic modalities different from the current regimen.AbstractAcquisition of BCR::ABL1 fusion as a primary or secondary event and RUNX1::MECOM fusion independently is reported in de novo and therapy‐related MDS/AML, albeit with low frequency (<0.5%). Coexistence of BCR::ABL1 and MECOM translocation is known to cause leukemogenesis in animal models and progression towards blast crisis CML but not AML. Here we report a unique case of pediatric AML with concomitant BCR::ABL1 and RUNX1::MECOM fusion.Routine diagnostic work‐up included WBC manual differential, immunophenotype, morphology, qPCR, FISH, and NGS‐based CNV analyses. The patient presented with history of fever, dizziness, fatigue, gingival bleeding, and epistaxis associated with ecchymosis in right hand and heavy, prolonged menstrual period. At presentation, her hemoglobin was 5.3 g/dL, WBC 52.1(10*9/L), PLT 10(10*9/L), ESR 5 mm/h and LDH 2658 U/L. Bone marrow was hypercellular with 71% blasts, and flow cytometry showed myeloid markers including CD11c, CD33, CD34, and CD45 among others indicating AML with monocytic differentiation. FISH analyses showed variant t(9;22) (q34.1;q11.1), one additional copy each of chromosome 8 and Runx1 gene, while NGS‐based CNV analyses revealed a terminal and proximal pathogenic gain within 9q34.12q34.3 and 22q11.1q11.23, respectively, and gain of entire chromosome 8 and 12 in mosaic state. qPCR confirmed the presence of p190 and also revealed RUNX1::MECOM fusion. Patient received ADE (cytarabine, daunorubicin, and etoposide) induction regimen but required multiple ICU admissions due to sepsis, cardiac shock, acute myocarditis, and thyroiditis. Coexisting BCR::ABL1 and RUNX1::MECOM fusion is suggestive of poor prognosis, and a need for consensus on the treatment modalities other than the current regimen is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“… 1 It is now thought that the RUNX1::MECOM fusion transcript contributes directly to leukemogenesis or leukemic transformation. 14 , 15 , 16 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A rare presentation of BCR‐ABL1 and RUNX1‐MECOM rearrangement in a pediatric patient with acute myeloid leukemia

Alamri,

Alanazi,

AlRajeh

et al. 2024

Clinical Case Reports

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“…MECOM is a well-known oncogene involved in cell proliferation and apoptosis and reported to be overexpressed in e.g. leukemia 62 , 81 , ovarian cancer 82 , and glioblastoma 83 . Again, the observed increased gene body methylation of MECOM was associated with decreased expression in intracranial metastases, which may contribute to differences in metastasis manifestation and progression between intra- and extracranial metastases.…”

Section: Discussionmentioning

confidence: 99%

Patient-specific identification of genome-wide DNA-methylation differences between intracranial and extracranial melanoma metastases

Kraft

Grützmann

Meinhardt

et al. 2023

Sci Rep

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Melanomas frequently metastasize to distant organs and especially intracranial metastases still represent a major clinical challenge. Epigenetic reprogramming of intracranial metastases is thought to be involved in therapy failure, but so far only little is known about patient-specific DNA-methylation differences between intra- and extracranial melanoma metastases. Hierarchical clustering of the methylomes of 24 patient-matched intra- and extracranial melanoma metastases pairs revealed that intra- and extracranial metastases of individual patients were more similar to each other than to metastases in the same tissue from other patients. Therefore, a personalized analysis of each metastases pair was done by a Hidden Markov Model to classify methylation levels of individual CpGs as decreased, unchanged or increased in the intra- compared to the extracranial metastasis. The predicted DNA-methylation alterations were highly patient-specific differing in the number and methylation states of altered CpGs. Nevertheless, four important general observations were made: (i) intracranial metastases of most patients mainly showed a reduction of DNA-methylation, (ii) cytokine signaling was most frequently affected by differential methylation in individual metastases pairs, but also MAPK, PI3K/Akt and ECM signaling were often altered, (iii) frequently affected genes were mainly involved in signaling, growth, adhesion or apoptosis, and (iv) an enrichment of functional terms related to channel and transporter activities supports previous findings for a brain-like phenotype. In addition, the derived set of 17 signaling pathway genes that distinguished intra- from extracranial metastases in more than 50% of patients included well-known oncogenes (e.g. PRKCA, DUSP6, BMP4) and several other genes known from neuronal disorders (e.g. EIF4B, SGK1, CACNG8). Moreover, associations of gene body methylation alterations with corresponding gene expression changes revealed that especially the three signaling pathway genes JAK3, MECOM, and TNXB differ strongly in their expression between patient-matched intra- and extracranial metastases. Our analysis contributes to an in-depth characterization of DNA-methylation differences between patient-matched intra- and extracranial melanoma metastases and may provide a basis for future experimental studies to identify targets for new therapeutic approaches.

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Chromosomal and Genomic Alterations in Pediatric AML

Lamble,

Huang

2024

Pediatric Oncology

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MECOM gene overexpression in pediatric patients with acute myeloid leukemia

Cited by 6 publications

References 20 publications

A rare presentation of BCR‐ABL1 and RUNX1‐MECOM rearrangement in a pediatric patient with acute myeloid leukemia

A rare presentation of BCR‐ABL1 and RUNX1‐MECOM rearrangement in a pediatric patient with acute myeloid leukemia

Patient-specific identification of genome-wide DNA-methylation differences between intracranial and extracranial melanoma metastases

Chromosomal and Genomic Alterations in Pediatric AML

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