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Leukemia Research Reports 2024A 67-year-old female came to Tampa General Hospital with Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) featuring an intriguing combination of...
A 67-year-old female came to Tampa General Hospital with Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) featuring an intriguing combination of mutations, including and mutations. Novel combination therapy with azacitidine, venetoclax and ponatinib allowed her to successfully achieve a complete response (CR) and undergo an allogeneic hematopoietic stem cell transplant (HSCT). This case report provides an overview of her clinical course, emphasizing the significance of integrated therapy and the challenges associated with balancing treatment for AML. It also underscores the importance of a multidisciplinary approach and careful monitoring of patients with complex hematologic conditions.
PubMed: 38736691
DOI: 10.1016/j.lrr.2024.100461 -
Cancers Apr 2024Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in the regulation of apoptosis.... (Review)
Review
Survivin was initially identified as a member of the inhibitor apoptosis (IAP) protein family and has been shown to play a critical role in the regulation of apoptosis. More recent studies showed that survivin is a component of the chromosome passenger complex and acts as an essential mediator of mitotic progression. Other potential functions of survivin, such as mitochondrial function and autophagy, have also been proposed. Survivin has emerged as an attractive target for cancer therapy because its overexpression has been found in most human cancers and is frequently associated with chemotherapy resistance, recurrence, and poor survival rates in cancer patients. In this review, we discuss our current understanding of how survivin mediates various aspects of malignant transformation and drug resistance, as well as the efforts that have been made to develop therapeutics targeting survivin for the treatment of cancer.
PubMed: 38730657
DOI: 10.3390/cancers16091705 -
Cancers Apr 2024The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key...
The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the use of an automated tool may reduce variability, improving the uniformity of the evaluation. The aim of this work is to develop an accurate AI-based tool for the automated quantification of cellularity in BMB histology. A total of 55 BMB histological slides, diagnosed as Ph- MPN between January 2018 and June 2023 from the archives of the Pathology Unit of University "Luigi Vanvitelli" in Naples (Italy), were scanned on Ventana DP200 or Epredia P1000 and exported as whole-slide images (WSIs). Fifteen BMBs were randomly selected to obtain a training set of AI-based tools. An expert pathologist and a trained resident performed annotations of hematopoietic tissue and adipose tissue, and annotations were exported as .tiff images and .png labels with two colors (black for hematopoietic tissue and yellow for adipose tissue). Subsequently, we developed a semantic segmentation model for hematopoietic tissue and adipose tissue. The remaining 40 BMBs were used for model verification. The performance of our model was compared with an evaluation of the cellularity of five expert hematopathologists and three trainees; we obtained an optimal concordance between our model and the expert pathologists' evaluation, with poorer concordance for trainees. There were no significant differences in cellularity assessments between two different scanners.
PubMed: 38730640
DOI: 10.3390/cancers16091687 -
Medicine May 2024The Philadelphia chromosome (Ph) is seen in most patients with chronic myeloid leukemia and some patients with acute lymphoblastic leukemia. However, Ph-positive acute... (Review)
Review
Philadelphia chromosome-positive acute myeloid leukemia successfully treated by allogeneic hematopoietic stem cell transplantation: A case report and review of the literature.
RATIONAL
The Philadelphia chromosome (Ph) is seen in most patients with chronic myeloid leukemia and some patients with acute lymphoblastic leukemia. However, Ph-positive acute myeloid leukemia (Ph + AML) is a rare entity with a poor prognosis and a short median survival period. To date, there have been few clinical reports on this disease. And the treatment regimen of this disease has not been uniformly determined.
PATIENT CONCERNS
We report a case of a Ph + AML. A 32-year-old male who was admitted to our hospital with weakness for 2 months.
DIAGNOSIS
Philadelphia chromosome-positive acute myeloid leukemia.
INTERVENTIONS
The patient achieved complete remission by the administration of a tyrosine kinase inhibitor, combined with low-intensity chemotherapy and a B-cell lymphoma 2 inhibitor. Then, allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his sister was successfully performed.
OUTCOMES
The patient has been in a continuous remission state for 6 months after transplantation.
LESSONS
We reported a rare Ph + AML case, successfully treated with allo-HSCT. This case provided strong support for treating Ph + AML with allo-HSCT.
Topics: Humans; Male; Hematopoietic Stem Cell Transplantation; Adult; Leukemia, Myeloid, Acute; Philadelphia Chromosome; Transplantation, Homologous; Remission Induction
PubMed: 38728478
DOI: 10.1097/MD.0000000000038110 -
Disease Markers 2024Chronic myeloid leukemia (CML) or chronic granulocytic leukemia is a myeloproliferative neoplasm indicated by the presence of the Philadelphia (Ph+) chromosome....
BACKGROUND
Chronic myeloid leukemia (CML) or chronic granulocytic leukemia is a myeloproliferative neoplasm indicated by the presence of the Philadelphia (Ph+) chromosome. First-line tyrosine kinase inhibitor, imatinib, is the gold standard for treatment. However, there has been known unresponsiveness to treatment, especially due to the involvement of other genes, such as the Janus kinase 2 (JAK2) gene. This study aimed to evaluate the relationships between JAK2 levels and complete hematological response (CHR), as well as early molecular response (EMR) after 3 months of imatinib treatment in patients with chronic phase CML.
METHODS
Patients with Ph+ CML in the chronic phase ( = 40; mean age, 40 ± 11 years) were recruited to complete assessments consisting of clinical examination and blood test, including evaluation of complete blood counts and the JAK2 levels, at baseline and following 3 months of therapy with imatinib (at an oral dose of 400 mg per day). Subjects were divided into two groups according to the presence of CHR and EMR.
RESULTS
JAK2 gene levels, phosphorylated, and total JAK2 proteins at baseline were significantly lower in the group with the presence of CHR and EMR. In addition, baseline JAK2 levels, including JAK2 gene expression, phosphorylated, and total JAK2 proteins, were negatively correlated with the presence of CHR and EMR.
CONCLUSIONS
Based on these findings, JAK2 levels may be a potential indicator for evaluating treatment response on imatinib due to its role in the pathophysiology of CML.
Topics: Humans; Imatinib Mesylate; Janus Kinase 2; Adult; Male; Female; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Middle Aged; Antineoplastic Agents; Protein Kinase Inhibitors; Biomarkers, Tumor; Treatment Outcome
PubMed: 38716474
DOI: 10.1155/2024/2906566 -
Scientific Reports May 2024Mammals are generally resistant to Mycobacterium avium complex (MAC) infections. We report here on a primary immunodeficiency disorder causing increased susceptibility...
Mammals are generally resistant to Mycobacterium avium complex (MAC) infections. We report here on a primary immunodeficiency disorder causing increased susceptibility to MAC infections in a canine breed. Adult Miniature Schnauzers developing progressive systemic MAC infections were related to a common founder, and pedigree analysis was consistent with an autosomal recessive trait. A genome-wide association study and homozygosity mapping using 8 infected, 9 non-infected relatives, and 160 control Miniature Schnauzers detected an associated region on chromosome 9. Whole genome sequencing of 2 MAC-infected dogs identified a codon deletion in the CARD9 gene (c.493_495del; p.Lys165del). Genotyping of Miniature Schnauzers revealed the presence of this mutant CARD9 allele worldwide, and all tested MAC-infected dogs were homozygous mutants. Peripheral blood mononuclear cells from a dog homozygous for the CARD9 variant exhibited a dysfunctional CARD9 protein with impaired TNF-α production upon stimulation with the fungal polysaccharide β-glucan that activates the CARD9-coupled C-type lectin receptor, Dectin-1. While CARD9-deficient knockout mice are susceptible to experimental challenges by fungi and mycobacteria, Miniature Schnauzer dogs with systemic MAC susceptibility represent the first spontaneous animal model of CARD9 deficiency, which will help to further elucidate host defense mechanisms against mycobacteria and fungi and assess potential therapies for animals and humans.
Topics: Animals; CARD Signaling Adaptor Proteins; Dogs; Genetic Predisposition to Disease; Mycobacterium avium-intracellulare Infection; Mycobacterium avium Complex; Genome-Wide Association Study; Dog Diseases; Sequence Deletion; Pedigree; Female; Male; Whole Genome Sequencing; Homozygote; Lectins, C-Type
PubMed: 38710903
DOI: 10.1038/s41598-024-61054-x -
Haematologica May 2024Not available.
Minimal residual disease monitoring in childhood Philadelphia chromosome-positive acute lymphoblastic leukemia: prognostic significance and correlation between multiparameter flow cytometry and real-time quantitative polymerase chain reaction.
Not available.
PubMed: 38695139
DOI: 10.3324/haematol.2024.285119 -
G3 (Bethesda, Md.) Jun 2024In humans, the prevalence of congenital microphthalmia is estimated to be 0.2-3.0 for every 10,000 individuals, with nonocular involvement reported in ∼80% of cases....
In humans, the prevalence of congenital microphthalmia is estimated to be 0.2-3.0 for every 10,000 individuals, with nonocular involvement reported in ∼80% of cases. Inherited eye diseases have been widely and descriptively characterized in dogs, and canine models of ocular diseases have played an essential role in unraveling the pathophysiology and development of new therapies. A naturally occurring canine model of a syndromic disorder characterized by microphthalmia was discovered in the Portuguese water dog. As nonocular findings included tooth enamel malformations, stunted growth, anemia, and thrombocytopenia, we hence termed this disorder Canine Congenital Microphthalmos with Hematopoietic Defects. Genome-wide association study and homozygosity mapping detected a 2 Mb candidate region on canine chromosome 4. Whole-genome sequencing and mapping against the Canfam4 reference revealed a Short interspersed element insertion in exon 2 of the DNAJC1 gene (g.74,274,883ins[T70]TGCTGCTTGGATT). Subsequent real-time PCR-based mass genotyping of a larger Portuguese water dog population found that the homozygous mutant genotype was perfectly associated with the Canine Congenital Microphthalmos with Hematopoietic Defects phenotype. Biallelic variants in DNAJC21 are mostly found to be associated with bone marrow failure syndrome type 3, with a phenotype that has a certain degree of overlap with Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, Diamond-Blackfan anemia, and reports of individuals showing thrombocytopenia, microdontia, and microphthalmia. We, therefore, propose Canine Congenital Microphthalmos with Hematopoietic Defects as a naturally occurring model for DNAJC21-associated syndromes.
Topics: Animals; Dogs; Microphthalmos; Disease Models, Animal; Genome-Wide Association Study; Phenotype; Genotype; Homozygote; Dog Diseases; Syndrome; Female; Male
PubMed: 38682429
DOI: 10.1093/g3journal/jkae067 -
BMC Cancer Apr 2024In low-income countries there is insufficient evidence on hematological, clinical, cytogenetic and molecular profiles among new CML patients. Therefore, we performed...
Hematological, clinical, cytogenetic and molecular profiles of confirmed chronic myeloid leukemia patients at presentation at a tertiary care teaching hospital in Addis Ababa, Ethiopia: a cross-sectional study.
BACKGROUND
In low-income countries there is insufficient evidence on hematological, clinical, cytogenetic and molecular profiles among new CML patients. Therefore, we performed this study among newly confirmed CML patients at Tikur Anbesa Specialized Hospital (TASH), Ethiopia.
OBJECTIVE
To determine the hematological, clinical, cytogenetic and molecular profiles of confirmed CML patients at tertiary care teaching hospital in Addis Ababa, Ethiopia.
METHODS
A facility-based cross-sectional study was conducted to evaluate hematological, clinical, cytogenetic and molecular profiles of confirmed CML patients at TASH from August 2021 to December 2022. A structured questionnaire was used to collect the patients' sociodemographic information, medical history and physical examination, and blood samples were also collected for hematological, cytogenetic and molecular tests. Descriptive statistics were used to analyze the sociodemographic, hematological, clinical, cytogenetic and molecular profiles of the study participants.
RESULTS
A total of 251 confirmed new CML patients were recruited for the study. The majority of patients were male (151 [60.2%]; chronic (CP) CML, 213 [84.7%]; and had a median age of 36 years. The median (IQR) WBC, RBC, HGB and PLT counts were 217.7 (155.62-307.4) x10/µL, 3.2 (2.72-3.6) x10/µL, 9.3 (8.2-11) g/dl and 324 (211-499) x 10/µL, respectively. All patients had leukocytosis, and 92.8%, 95.6% and 99.2% of the patients developed anemia, hyperleukocytosis and neutrophilia, respectively. Fatigue, abdominal pain, splenomegaly and weight loss were the common signs and symptoms observed among CML patients. Approximately 86.1% of the study participants were Philadelphia chromosome positive (Ph+) according to fluorescence in situ hybridization (FISH). P210, the major breakpoint protein, transcript was detected by both qualitative polymerase chain reaction (PCR) and quantitative real time polymerase chain reaction (PCR).
CONCLUSION
During presentation, most CML patients presented with hyperleukocytosis, neutrophilia and anemia at TASH, Addis Ababa. Fatigue, abdominal pain, splenomegaly and weight loss were the most common signs and symptoms observed in the CML patients. Most CML patients were diagnosed by FISH, and p120 was detected in all CML patients diagnosed by PCR. The majority of CML patients arrive at referral center with advanced signs and symptoms, so better to decentralize the service to peripheral health facilities.
Topics: Humans; Male; Cross-Sectional Studies; Female; Ethiopia; Adult; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hospitals, Teaching; Middle Aged; Young Adult; Adolescent; Tertiary Care Centers; Aged; Cytogenetic Analysis; Fusion Proteins, bcr-abl; Tertiary Healthcare
PubMed: 38664756
DOI: 10.1186/s12885-024-12282-x