Two novel high-risk adult B-cell acute lymphoblastic leukemia subtypes with high expression of CDX2 and IDH1/2 mutations

Blood ◽  
2021 ◽  
Author(s):  
Takahiko Yasuda ◽  
Masashi Sanada ◽  
Masahito Kawazu ◽  
Shinya Kojima ◽  
Shinobu Tsuzuki ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
High Expression ◽  
Sequencing Analysis ◽  
Chromosome 1Q ◽  
Disease Outcomes ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Disease Stratification

The genetic basis of leukemogenesis in adults with B-cell acute lymphoblastic leukemia (B-ALL) is largely unclear and its clinical outcome remains unsatisfactory. This study aimed to advance the understanding of biological characteristics, improve disease stratification, and identify molecular targets of adult B-ALL. Adolescents and young adults (AYA; 15-39 years old, n = 193) and adults (40-64 years old, n = 161) with Philadelphia chromosome-negative B-ALL were included in this study. Integrated transcriptomic and genetic analyses were used to classify the cohort into defined subtypes. Of the 323 cases included in the RNA sequencing analysis, 278 (86.1%) were classified into 18 subtypes. The ZNF384 subtype (22.6%) was the most prevalent, with two novel subtypes (CDX2-high and IDH1/2-mut) identified among cases not assigned to the established subtypes. The CDX2-high subtype (3.4%) was characterized by high expression of CDX2 and recurrent gain of chromosome 1q. The IDH1/2-mut subtype (1.9%) was defined by IDH1 R132C or IDH2 R140Q mutations with specific transcriptional and high-methylation profiles. Both subtypes showed poor prognosis and were considered inferior prognostic factors independent of clinical parameters. Comparison with a previously reported pediatric B-ALL cohort (n = 1003) showed that the frequencies of these subtypes were significantly higher in AYA/adults than in children. We delineated the genetic and transcriptomic landscape of adult B-ALL and identified two novel subtypes that predict poor disease outcomes. Our findings highlight the age-dependent distribution of subtypes, which partially accounts for the prognostic differences between adult and pediatric B-ALL.

scholarly journals A novel BCR-ABL1 mutation in a patient with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia

2018 ◽  
Vol Volume 11 ◽  
pp. 8589-8598 ◽  
Author(s):  
Raquel Vinhas ◽  
Alexandra Lourenço ◽  
Susana Santos ◽  
Marcos Lemos ◽  
Patrícia Ribeiro ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Philadelphia Chromosome Positive

Clinical features and outcome of B-cell acute lymphoblastic leukemia in patients older than 9 years: A single center experience of 241 cases from AIIMS, New Delhi, India.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7082-7082 ◽  
Author(s):  
Atul Sharma ◽  
Sunu Lazar Cyriac ◽  
Siddharth Kumar Sahai ◽  
Sameer Bakhshi ◽  
Ritu Gupta ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Age Groups ◽  
Outcome Analysis ◽  
Total Leucocyte Count ◽  
Age Group ◽  
Single Center ◽  
Cell Acute Lymphoblastic Leukemia

7082 Background: Data on B cell Acute Lymphoblastic leukemia (ALL) in the poor prognostic age group of > 9 years from India is minimal. Methods: This is an analysis of patients of above 9 years that were diagnosed and treated from January 2000 to December 2010 at a single institute . All patients who completed at least 4 weeks of induction therapy were analysed for various outcomes. Results: Of the 241 newly registered patients, the median age was 19 years (Range 10-78 years) with an M:F ratio of 1.9:1. Out of this 47%, 25% & 28% patients belonged to 10-18, 19-30 & > 31 years age group respectively. Twenty seven (11.6%) and 5(2%) had CSF and testicular involvement respectively. Thirty nine per cent had a total leucocyte count (TLC) of above 30x109/L. Philadelphia chromosome (Ph) positivity was seen in 27% and was equally distributed among the different age groups. Patients available for outcome analysis were 213(88.4%). Complete remission rate (CRR) was 66.6% and induction mortality was 26.3%.At a median follow up of 65.8 months 5 year leukemia free survival was 30.5%. Seventy eight (55%) patients relapsed (median relapse time of 13.5 months, range 1.7 to 53.4 months) , 55% during maintenance phase. The 5 year overall survival (OS) was 30.3% with a median OS of 15.8 months. The OS was similar in 10-18 and 19-30 age groups (5 year OS 35% vs. 27.5%, p=0.641) but it was significantly lower in >31 years (5year OS 21%, p=0.008). Apart from this, extramedullary disease, not attaining a CR in 1st induction, albumin at presentation below 3.5gm% and TLC of >100x109/L were significant poor prognostic markers for survival. Conclusions: This is a large study of B-ALL outcomes in patients above 9 years from a single center in India. Patients above 30 years had a worse prognosis while the prognosis of 10-18 and 19-30 years age group were similar. Induction mortality was higher mainly because of advanced disease and poor performance status at presentation.

scholarly journals RAG1 high expression associated with IKZF1 dysfunction in adult B-cell acute lymphoblastic leukemia

2019 ◽  
Vol 10 (16) ◽  
pp. 3842-3850 ◽  
Author(s):  
Qi Han ◽  
Jinlong Ma ◽  
Yan Gu ◽  
Huihui Song ◽  
Malika Kapadia ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
High Expression ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages

2015 ◽  
Vol 112 (13) ◽  
pp. 4074-4079 ◽  
Author(s):  
James Scott McClellan ◽  
Christopher Dove ◽  
Andrew J. Gentles ◽  
Christine E. Ryan ◽  
Ravindra Majeti
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Lineage Reprogramming ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Differentiation Block ◽  
Factor C ◽  
And Function

BCR–ABL1+ precursor B-cell acute lymphoblastic leukemia (BCR–ABL1+ B-ALL) is an aggressive hematopoietic neoplasm characterized by a block in differentiation due in part to the somatic loss of transcription factors required for B-cell development. We hypothesized that overcoming this differentiation block by forcing cells to reprogram to the myeloid lineage would reduce the leukemogenicity of these cells. We found that primary human BCR–ABL1+ B-ALL cells could be induced to reprogram into macrophage-like cells by exposure to myeloid differentiation-promoting cytokines in vitro or by transient expression of the myeloid transcription factor C/EBPα or PU.1. The resultant cells were clonally related to the primary leukemic blasts but resembled normal macrophages in appearance, immunophenotype, gene expression, and function. Most importantly, these macrophage-like cells were unable to establish disease in xenograft hosts, indicating that lineage reprogramming eliminates the leukemogenicity of BCR–ABL1+ B-ALL cells, and suggesting a previously unidentified therapeutic strategy for this disease. Finally, we determined that myeloid reprogramming may occur to some degree in human patients by identifying primary CD14+ monocytes/macrophages in BCR–ABL1+ B-ALL patient samples that possess the BCR–ABL1+ translocation and clonally recombined VDJ regions.

High expression of Musashi-2 indicates poor prognosis in adult B-cell acute lymphoblastic leukemia

2013 ◽  
Vol 37 (8) ◽  
pp. 922-927 ◽  
Author(s):  
Qitian Mu ◽  
Yungui Wang ◽  
Bing Chen ◽  
Wenbin Qian ◽  
Haitao Meng ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Poor Prognosis ◽  
Lymphoblastic Leukemia ◽  
High Expression ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals High expression of LMO2 predicts a favorable outcome in adult patients with BCR/ABL negative B-cell acute lymphoblastic leukemia

2016 ◽  
Vol 11 (3) ◽  
pp. 1917-1922
Author(s):  
RABAB M. ALY ◽  
MONA M. TAALAB ◽  
EMAN M. ABDSALAM ◽  
OMAR H. ELYAMANY ◽  
OMAR E. HASAN
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Favorable Outcome ◽  
High Expression ◽  
Cell Acute Lymphoblastic Leukemia
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