MLL-SEPT5 Fusion Transcript in Myelodysplastic Syndrome Patient With t(11;22)(q23;q11)

Objectives: This study aimed to identify unknown mixed lineage leukemia (MLL) translocation partner genes in a de novo patient with myelodysplastic syndrome (MDS) with t(11;22)(q23;q11) and investigate the clinical and molecular features of this patient.Methods: Bone marrow cells were assessed by karyotype analysis to reveal chromosomal abnormalities. Fluorescence in situ hybridization (FISH) was performed to detect MLL gene rearrangement using an MLL-specific break-apart probe. LDI-PCR and RT-PCR were performed, and the PCR products were sequenced using an Illumina MiSeq sequencer (Illumina, San Diego, CA, USA). The sequence data of the PCR products were analyzed using bioinformatics tools. Meanwhile, clinical data were collected to evaluate the prognosis of the patient.Results: Chromosomal karyotype analysis showed that the karyotype of the patient was 46, XX, t(11;22)(q23;q11)[10]/46, XX[1]. Subsequently, FISH data confirmed MLL gene rearrangement in the patient. LDI-PCR precisely showed that SEPT5 was the MLL translocation partner gene. RT-PCR and sequencing analysis disclosed the presence of MLL-SEPT5 fusion transcript and confirmed the fusion between MLL exon 8 and SEPT5 exon 3. Moreover, the patient had a recurrence shortly after allogeneic hematopoietic stem cell transplantation.Conclusion: Although the MLL-SEPT5 fusion transcript was occasionally described in acute myeloid leukemia, it was first identified in MDS. Patients with MLL-SEPT5 fusion gene exhibited a poor prognosis even with an aggressive treatment.

Drug Repurposing for Targeting Acute Leukemia With KMT2A (MLL)—Gene Rearrangements

The treatment failure rates of acute leukemia with rearrangements of the Mixed Lineage Leukemia (MLL) gene highlight the need for novel therapeutic approaches. Taking into consideration the limitations of the current therapies and the advantages of novel strategies for drug discovery, drug repurposing offers valuable opportunities to identify treatments and develop therapeutic approaches quickly and effectively for acute leukemia with MLL-rearrangements. These approaches are complimentary to de novo drug discovery and have taken advantage of increased knowledge of the mechanistic basis of MLL-fusion protein complex function as well as refined drug repurposing screens. Despite the vast number of different leukemia associated MLL-rearrangements, the existence of common core oncogenic pathways holds the promise that many such therapies will be broadly applicable to MLL-rearranged leukemia as a whole.

Immunophenotyping and cytogenetic profile of children with acute lymphoblastic leukemia: A study from a tertiary care center from Kashmir.

Background The complete cytogenetic and immunophenotyping data in children suffering from acute lymphoblastic leukemia (ALL) in Jammu and Kashmir is scarce. To bridge this knowledge gap the present study proposes to evaluate the immunophenotype and cytogenetic profile of pediatric ALL patients treated in our hospital. Material and methods This hospital-based observational study was conducted on 180 pediatric patients aged between 1 to 18 years who had visited the Paediatric unit of the Department of Medical Oncology at Sher-I -Kashmir Institute of Medical Science, Srinagar ,Jammu and Kashmir between the January 2015 to December 2019. Result Among the study participants, 57.8% were male and 42.2% were female with a mean age of 9.24 years and median of 8 Years. Among the participants, 57.2% were below 10 years of age and 42.8% were above 10years of age. CNS disease was reported in 7.8% of the study participants. 63.3% patients had a TLC count of less than 20000. Immunophenotyping data revealed pre-B ALL in 77.8% of children. Cytogenetic study was conducted on 153 patients among them 74.4% had a normal karyotype, 7.2% s had hyperdiploidy and 3.3% had hypodiploidy. The FISH analysis showed that 23.3% of study participants were positive for the TEL-AML study, 11.1% were positive for BCR-ABL analysis and 4.4% of participants were positive for MLL gene analysis. The overall survival in the study population was 78.9% among the study participants. Only the MLL gene rearrangement analysis showed a statistically significant correlation with the survival analysis (P<0.5). Conclusion In summary, the present study reported the complete cytogenetic and immunophenotyping profile of the children suffering from acute lymphoblastic leukemia in Jammu and Kashmir.