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Cureus Jan 2022Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation... (Review)
Review
Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation that is thought to occur spontaneously. CML could potentially lead to the development of myeloid sarcoma (MS), which is a rare neoplasm composed of immature myeloid cells that could evolve into a tumor mass at any anatomical site other than the bone marrow. MS can develop spontaneously or as a result of another form of myeloid neoplasm. Most instances of CML precede blast phase (BP) within two to three years after the first diagnosis of CML chronic phase (CP) at the age of pre-tyrosine kinase inhibitor (TKI) treatment. MS developing in CML patients during the era of TKI treatment is infrequently mentioned in the literature, primarily in single-case studies. As a result, the prognostic influence of MS in CML patients has not been well investigated. In the age of TKI treatment, it is uncertain whether MS and medullary BP have comparable clinical and prognostic relevance. The precise diagnosis of MS is critical for effective treatment, which is frequently delayed due to a high risk of misdiagnosis. This review focuses on the relationship between the development of MS from CML, and it culminates with recommendations for future hematology practice. A literature search was conducted in multiple databases, and the studies were appraised based on the inclusion and exclusion criteria. Finally, studies to date have shown that the existence of CML and its possible progression to MS in individuals map out the numerous implications this disease has in hematology practice. Though occurrences are uncommon in general, the prognosis for patients is bleak, necessitating the exploration and implementation of diagnostic and therapy advancements. Because there is limited evidence in the literature on its existence in the medullary chronic phase and outcomes in the era of TKI, it must be carefully investigated because it might be the first symptom of progressive illness prior to hematological progression.
PubMed: 35036234
DOI: 10.7759/cureus.21077 -
International Journal of Hematology Dec 2023Myeloid sarcoma is a rare clinical entity that presents as an isolated proliferation of leukemic cells, concurrently with or at relapse of acute myeloid leukemia (AML),... (Review)
Review
Myeloid sarcoma is a rare clinical entity that presents as an isolated proliferation of leukemic cells, concurrently with or at relapse of acute myeloid leukemia (AML), myelodysplastic syndromes/neoplasms (MDS), chronic myeloid leukemia (CML), and myeloproliferative neoplasm (MPN). Myeloid sarcoma disrupts the normal architecture of its surrounding tissues. When it forms in long bones, it can cause their pathological fracture. We recently experienced a rare case of MDS presenting with myeloid sarcoma in the femur that eventually resulted in its pathological fracture. Detailed chromosomal analysis of the bone marrow cells suggested emergence of myeloid sarcoma during the fast-paced progression of MDS just after acquiring trisomy 22. A comprehensive review of previous cases of myeloid sarcoma-associated pathological fracture indicated possible involvement of structural rearrangements of chromosomes 9 and 22. Management of myeloid sarcoma should continue to improve, and clinicians should note that myeloid sarcoma with specific chromosomal alterations needs extra medical attention to prevent pathological fracture.
Topics: Humans; Sarcoma, Myeloid; Fractures, Spontaneous; Myeloproliferative Disorders; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
PubMed: 37707761
DOI: 10.1007/s12185-023-03656-1 -
Frontiers in Oncology 2023
PubMed: 37434976
DOI: 10.3389/fonc.2023.1223296 -
Radiology and Oncology Mar 2019Background Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a solid tumor of extramedullary localization composed of malignant primitive myeloid...
Background Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a solid tumor of extramedullary localization composed of malignant primitive myeloid cells. The purpose of the study was to identify clinical and imaging features in a large patient sample. Patients and methods Overall, 71 cases (34 females (47.9%) and 37 males (52.1%) with a median age of 56 (± 16 years) of histopathologically confirmed myeloid sarcoma were included into this study. The underlying hematological disease, occurrence, localizations and clinical symptoms as well as imaging features on computed tomography and magnetic resonance imaging were investigated. Results In 4 cases (5.63%) the manifestation of MS preceded the systemic hematological disease by a mean value of 3.8 ± 2.1 months. In 13 cases, first presentation of MS occurred simultaneously with the initial diagnosis of leukemia, and 51 patients presented MS after the initial diagnosis of the underlying malignancy with a mean latency of 39.8 ± 44.9 SD months. The visceral soft tissue was affected in 26 cases, followed by the cutis/subcutis was affected in 21 cases. Further localizations were bones (n = 13), central nervous system (n = 9), lymph nodes (n = 4) and visceral organs (n = 9). Conclusions MS is a rare complication of several hematological malignancies, predominantly of acute myeloid leukemia, which can affect any part of the body. In most cases it occurs after the diagnosis of the underlying malignancy, and affects frequently the cutis and subcutis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Male; Middle Aged; Prodromal Symptoms; Sarcoma, Myeloid; Time Factors; Tomography, X-Ray Computed; Young Adult
PubMed: 30893056
DOI: 10.2478/raon-2019-0014 -
Nature Chemical Biology Jan 2020The post-genomic era has seen many advances in our understanding of cancer pathways, yet resistance and tumor heterogeneity necessitate multiple approaches to target...
The post-genomic era has seen many advances in our understanding of cancer pathways, yet resistance and tumor heterogeneity necessitate multiple approaches to target even monogenic tumors. Here, we combine phenotypic screening with chemical genetics to identify pre-messenger RNA endonuclease cleavage and polyadenylation specificity factor 3 (CPSF3) as the target of JTE-607, a small molecule with previously unknown target. We show that CPSF3 represents a synthetic lethal node in a subset of acute myeloid leukemia (AML) and Ewing's sarcoma cancer cell lines. Inhibition of CPSF3 by JTE-607 alters expression of known downstream effectors in AML and Ewing's sarcoma lines, upregulates apoptosis and causes tumor-selective stasis in mouse xenografts. Mechanistically, it prevents the release of newly synthesized pre-mRNAs, resulting in read-through transcription and the formation of DNA-RNA hybrid R-loop structures. This study implicates pre-mRNA processing, and specifically CPSF3, as a druggable target providing an avenue to therapeutic intervention in cancer.
Topics: Animals; Apoptosis; Binding Sites; Carboxylic Ester Hydrolases; Cell Line, Tumor; Cell Survival; Cleavage And Polyadenylation Specificity Factor; HEK293 Cells; Humans; Leukemia, Myeloid, Acute; Male; Mass Spectrometry; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Phenotype; Phenylalanine; Piperazines; Protein Binding; RNA Precursors; RNA, Messenger; RNA, Small Interfering; Sarcoma, Ewing
PubMed: 31819276
DOI: 10.1038/s41589-019-0424-1 -
Leukemia & Lymphoma Dec 2021Myeloid sarcoma (MS) in the setting of concomitant medullary AML is relatively well described, while much less is known about patients presenting with MS with <20% bone...
Myeloid sarcoma (MS) in the setting of concomitant medullary AML is relatively well described, while much less is known about patients presenting with MS with <20% bone marrow blasts. We conducted a retrospective analysis of 56 patients with MS with <20% marrow blasts seen at MD Anderson between 2005 and 2020. The prevalence of MS without medullary AML was 1.4% among all newly diagnosed AML patients. The majority (75%) of patients had a single known anatomic site involved, with the skin (34%) being the most frequent. The most common histologic subtype was monocytic, and 11% of patients had a known history of an antecedent hematologic disorder. The majority of patients (70%) received frontline intensive chemotherapy induction, with 75% of those evaluable attaining complete or partial responses. The median overall survival (OS) and event-free survival (EFS) were 3.41 and 3.07 years, respectively. Patients with bone marrow blasts of ≥5% or medullary relapse had inferior outcomes, while age (>60 years) was not associated with outcomes. There was a suggestion that patients with isolated leukemia cutis may have had better outcomes compared to patients with other organ involvement, but this did not reach statistical significance. Most patients who had cytogenetic analysis had a diploid karyotype within their MS and bone marrow pathway mutations were enriched in MS at diagnosis, and at time of medullary relapse. Our study provides a large dataset summarizing the clinical and molecular analysis of patients with MS with <20% BM blasts and suggests that monitoring for medullary leukemia is important for early detection of relapse.
Topics: Bone Marrow; Humans; Leukemia, Myeloid, Acute; Middle Aged; Prognosis; Recurrence; Retrospective Studies; Sarcoma, Myeloid
PubMed: 34380367
DOI: 10.1080/10428194.2021.1961235 -
Cancers Feb 2023Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes.... (Review)
Review
Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to adult patients. Optimal treatment remains undefined, yet allogeneic hematopoietic stem cell transplantation (allo-HSCT) and epigenetic reprogramming in children are potential therapies. Importantly, the biology of MS development is poorly understood; however, cell-cell interactions, epigenetic dysregulation, cytokine signaling, and angiogenesis all appear to play key roles. This review describes pediatric-specific MS literature and the current state of knowledge about the biological determinants that drive MS development. While the significance of MS remains controversial, the pediatric experience provides an opportunity to investigate mechanisms of disease development to improve patient outcomes. This brings the hope of better understanding MS as a distinct disease entity deserving directed therapeutic approaches.
PubMed: 36900239
DOI: 10.3390/cancers15051443 -
Cancer Medicine Apr 2023Myeloid sarcoma (MS) is a rare, extramedullary tumor consisting of myeloid blasts. Little is known about the genetic background of MS and the prognostic value of genetic...
BACKGROUND
Myeloid sarcoma (MS) is a rare, extramedullary tumor consisting of myeloid blasts. Little is known about the genetic background of MS and the prognostic value of genetic abnormalities in MS. In particular, the broad variety of gene fusions that occur in MS is marginally covered by traditional testing methods due to lack of fresh tumor specimens.
METHODS
Here, we analyzed the clinical and genetic features of 61 MS cases. We performed RNA sequencing (RNA-seq) on formalin-fixed paraffin-embedded (FFPE) or fresh samples to analyze fusion genes in 26 cases. In addition, we performed genetic abnormalities-based risk stratification using fusion genes and gene mutations.
RESULTS
A total of 305 fusion genes were identified in 22 cases, including the following five recurrent fusion genes: RUNX1-RUNX1T1, CBFβ-MYH11, ETV6-MECOM, FUS-ERG, and PICALM-MLLT10. The prognosis in the adverse-risk group was significantly worse than that in the favorable/intermediate-risk group (median survival: 12 months vs. not reached; p = 0.0004).
CONCLUSION
These results indicated the efficacy of RNA-seq using FFPE-derived RNA as a clinical routine for detecting fusion genes, which can be used as markers for risk stratification in MS.
Topics: Humans; Sarcoma, Myeloid; Base Sequence; Mutation; Transcription Factors; Sequence Analysis, RNA; Oncogene Proteins, Fusion
PubMed: 36916780
DOI: 10.1002/cam4.5654 -
JACC. Case Reports Jun 2021A 53-year-old man with a background of acute myelomonocytic leukemia in remission presented with pleurisy. Repeat transthoracic echocardiography over several weeks...
A 53-year-old man with a background of acute myelomonocytic leukemia in remission presented with pleurisy. Repeat transthoracic echocardiography over several weeks revealed thickening left ventricular walls and decreasing systolic function. He died of decompensated heart failure due to cardiac myeloid sarcoma, with autopsy revealing an enlarged heart weighing >1 kg. ().
PubMed: 34317666
DOI: 10.1016/j.jaccas.2021.04.033 -
Clinical Ophthalmology (Auckland, N.Z.) 2022Acute myeloid leukemia (AML) is a hematological malignancy affecting different organ systems including the eye. The purpose of this review is to present and evaluate the... (Review)
Review
Acute myeloid leukemia (AML) is a hematological malignancy affecting different organ systems including the eye. The purpose of this review is to present and evaluate the medical literature regarding the early ophthalmological manifestations of acute myeloid leukemia. AML affects the ocular system through direct infiltration of tissues, secondary to hematological abnormalities, or in the form of chloroma or myeloid sarcoma in the brain or orbit consequently leading to a variety of manifestations depending on the ocular tissue involved. It is imperative for ophthalmologists to be aware of the early ophthalmological manifestations of AML which will allow for earlier diagnosis and treatment of this life-threatening disease.
PubMed: 35800672
DOI: 10.2147/OPTH.S342720