Leukemia Research Reports最新文献

Introduction

SAMD9L mutation has been associated with hematological malignancies. The mutation has diverse hematological phenotypes ranging from Myelodysplastic syndrome (MDS) to Acute myeloid leukemia (AML)involving chromosome 7 aberration and recently described the emerging phenotype of aplastic anemia. We report two siblings with SAMD9L germline mutation born to asymptomatic consanguineous parents. each with different hematological phenotype.

Methods

Case #1: A 7- year old girl presented with thrombocytopenia & 4% peripheral blasts. She has no dysmorphic features . Family history is negative for hematological malignancies or BMF. She was diagnosed with MDS- Monomsomy7 . She transformed to AML over few weeks During this period her sibling presented with aplastic anemia, his (WES) revealed germline SAMD9L mutation which was detected in his sister . During chemotherapy of AED; there was interrupted due to septic shock so She was bridged with (Azacitadine + Venetoclax) prior to haploidentical BMT Case#2: A10- week old male presented with respiratory symptoms. He was diagnosed with Aplastic anemia and CMV pneumonitis .He was not dysmorphic WES revealed germline SAMD9L Mutation. although normal immunology workup, Natural Killer cell dysfunction was suspected based on SAMD9L mutation detection, early age of presentation, & resistant CMV-Viremia. He was treated for CMV infection and decided for haploidentical BMT

Results

We suggest to include SAMD9/SAMD9L in the standard AMLMDS genetic panel if additional system involved like immunodeficiency, neurological or genitourinary anomaly.

Conclusions

the heterogeneity of SAMD9L mutation even in family. High index of suspicious of this germline mutation is warranted in children with MDS.

Introduction

Somatic or germline mutations in genes regulating Ras-MAPK pathway have been identified in majority of Juvenile myelomonocytic leukemia (JMML) cases. Mosaicism of KRAS and NRAS mutations in JMML were reported, with variation in the proportion of cells carrying these mutations across different organs. However, how this proportion is distributed across different organs had not been clarified whereas prevalence of somatic oncogenic KRAS mutations are known.

Methods

Our study focused on one JMML patient with mosaic KRAS G12D mutation and uniparental disomy at the 12p locus, who developed aggressive transformation, invasion into multiple organs and subsequently died. DNA from FFPE biopsy samples of eighteen organs were analyzed using mutation-specific digital PCR (dPCR). The variant allele frequency (VAF) of KRAS G12D and hetero SNP at the 12p locus were analyzed in each samples to remove the impact of mutation by infiltrating tumor cells and to estimate the percentage of KRAS mutant cells.

Results

KRAS G12D mutations were identified in samples from sixteen of eighteen analyzed tissues. The frequency of KRAS G12D mutated alleles varied among different tissue type and the median VAF was 5.9% (2.0% -29.3%). The VAF were relatively high in gastrointestinal tract (stomach, colon, ileum), liver and spleen, whereas the VAF were low or undetected in testis, heart and spinal cord.

Conclusions

Our findings suggest that KRAS mosaic mutations can exhibit tissue specificity like somatic oncogenic mutations. These tissue distribution might be associated with pathogenesis of JMML and other types of cancer with mosaicism.

Introduction

Luspatercept reduced the severity of anemia in transfusion-dependent lower risk MDS with ring sideroblasts (RS) in the MEDALIST trial. Here we present real-world data in a prospective multicenter registry study of MDS patients treated with luspatercept (ChiCTR2300071857). Patients who were not enrolled in the MEDALIST trial were also evaluated, including those of higher IPSS-R risk, without ring sideroblasts, or failed to prior hypomethylating agent (HMA) therapy.

Methods

Eligible patients were ≥ 18 years old and were RBC transfusion-dependent (defined as ≥2 units of RBC transfusion per 8 weeks). Primary endpoint was RBC transfusion independence (RBC-TI) for ≥8 weeks. Secondary endpoints are hematological improvement-erythroid (HI-E, defined as >50% reduction in RBC transfusion), neutrophil (HI-N) and platelet (HI-P) per the IWG 2006 criteria.

Results

From June 2022 to August 2023, 25 patients were treated with luspatercept for a median of 7 cycles (Table 1). The median follow-up time was 19.4 weeks. The rate of RBC-TI was 36%. The median duration of RBC-TI was 227 [IQR: 129-324] days. The rates of HI-E, HI-N, HI-P were 52% (13/25), 21% (3/14) and 33% (5/15), respectively. Multi-variant analysis revealed that lower transfusion burden (<6 u/8w) favored higher RBC-TI rate (OR: 0.041, 95% CI: 0.003∼0.666, p=0.025), while other characteristics such as IPSS-R risk, presence of RS or SF3B1 and prior therapy had no impact on the outcome (Table 1).

Conclusions

Our real-world data confirms the clinical benefit of luspatercept observed in the MEDALIST trial. Luspatercept retains efficacy in patients without RS, or failed to prior HMA therapy.

Patients with inflammatory bowel disease (IBD) are exposed to chronic systemic inflammation and are at risk for secondary malignancies. Here we review the literature on the risk of myeloid neoplasms (MN) in IBD and present the disease profiles of patients at a single institution with IBD who later developed MN, comparing them to those in the literature. No IBD characteristic was found to associate with MN disease severity, including the previously-identified association between MNs and thiopurine exposure. Of the somatic mutations identified in out cohort's MN, mutations in TET2 were most prevalent, followed by FLT3-ITD, BCR-ABL, and NPM1 mutations.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by the proliferation of plasmacytoid dendritic cells with a blast-like appearance. It usually presents in elderly people, and clinical manifestations include nodular blue-violet skin lesions, bone marrow infiltration and, less frequently, extramedullary involvement. Gynecological manifestation (breast mass and exocervical lesion) is an unusual and rare presentation.

Herein, we report the case of a 51-year-old woman patient who presented with a history of a rapidly growing and bleeding breast mass, along with a decline in general health. Notably, the disease had multifocal involvement, affecting the breast, uterine cervix, and cervical lymphadenopathy.

Biopsies were performed on the breast mass and cervical lesion. Histopathological examination showed a diffuse lymphoid proliferation. The neoplastic cells show immunoreactivity for CD45 and CD56.

The myelogram showed a 50 % excess of blasts with a heterogeneous appearance with the presence of cells that could suggest dendritic plasmacytoid cells. Bone marrow immunophenotyping showed the presence of blast-like cells that were positive for CD4, CD56, CD123, which supported the diagnosis of BPDCN.

Despite initiating chemotherapy, the patient's condition rapidly deteriorated, highlighting the aggressive nature of BDCP. This case underscores the importance of early detection and the need for further research to improve outcomes for this rare condition.

Both clonal plasma cell and myeloid disorders occur more frequently with age. Patients with concurrent clonal plasma cell and myeloid disorders (CPCMD) can present clinical and therapeutic challenges. In this single-institution cohort of patients with CPCMD (n = 18), we abstracted clinically relevant themes. A majority of patients (12/18) were treated with clone-directed therapies and three received treatment targeting both clones. Treatment of clones with targetable genetic lesions or those causing end-organ complications should be prioritized. Simultaneous treatment of both clones can be safe but is best done in a stepwise manner. Further study of patients with dual clonal processes is warranted.

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 NPM1 and IDH2 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.

Introduction

Recurrent somatic mutations are found in about 90 % of the MDS patients, and some of the mutations are known to have a prognostic value at various clinical stages of myelodysplastic syndrome (MDS). However, there are no specific guidelines for the assessment of CNAs, and the CNA test is not included in standard practice in the diagnosis and prognostication of MDS. Thus, there is a need to evaluate whether the detection of CNAs, in addition to genetic mutations, has clinical significance. In this study.

Methods

Targeted deep sequencing of 28 well-known MDS-related genes was performed for 266 patients with MDS. DNA copy number was estimated using the targeted deep sequencing data.

Results

Overall, 215 (80.8 %) patients were found to have at least one somatic mutation; 67 (25.2 %) had at least one CNA; 227 (85.3 %) had either a somatic mutation or CNA; and 12 had CNA without somatic mutations. Considering the clinical variables and somatic mutations alone, multivariate analysis demonstrated that sex, revised International Prognostic Scoring System (IPSS-R), and NRAS and TP53 mutations were independent prognostic factors for overall survival. For AML-free survival, these factors were sex, IPSS-R, and mutations in NRAS, DNMT3A, and complex karyotype/TP53 mutations. When we consider clinical variables along with somatic mutations and CNAs, genetic alterations in TET2, LAMB4, U2AF1, and CBL showed additional significant impact on the survivals.

Conclusions

In conclusion, our study suggests that the concurrent detection of somatic mutations and targeted CNAs may provide clinically useful information for the prognosis of MDS patients.

Introduction

In the absence of significant dysplasia in suspected myelodysplastic syndrome (MDS), flow cytometry (FC) analysis helps to distinguish clonal cytopenia. The aim of the study was to analyse the concordance of cytomorphological characteristics and flow cytometry in patients with newly diagnosed MDS in KB Merkur in the period from March 2016 to April 2023.

Methods

We analyzed bone marrow FC in 69 patients (38 men, 31 women) who were diagnosed with MDS based on bone marrow morphology.

Results

In 57 patients (82%), the morphological diagnosis of MDS was also confirmed in the flow cytometry findings. In 11 (91%) of a total of 12 patients in whom the FC analysis did not prove MDS, no blasts were observed in the cytological findings. The expression of CD34, CD117, CD13 and CD33 (cut off 20%) was analyzed in 57 patients in whom MDS was suspected in the myelogram and FC . CD117 and CD33 did not differ between groups, regardless of MDS subtype. CD34 and CD13 was statistically significantly higher in high-risk MDS than in low-risk MDS. There was no statistically significant difference in the level of hemoglobin and expression of CD antigen, while the level of platelets correlated negatively with the level of CD117, CD13 and CD34. The expression of CD34 positively correlated with the level of C reactive protein.

Conclusions

Flow cytometry in MDS is a valuable additional method in discriminating MDS from other forms of cytopenia to improve both diagnosis and prognosis, but there is a need to establish standard techniques in everyday use.