High CRLF2 Expression Could Identify Acute Lymphoblastic Leukemia Patients with Poor Outcome but Not IKZF1

2020 ◽  
Vol 0 (0) ◽  
pp. 1-8
Author(s):  
Layla Saleh ◽  
Nour Darwish ◽  
Sherin Abdel-Aziz ◽  
Dalia Salem ◽  
Noha Eisa ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Outcome

scholarly journals Detectable Molecular Residual Disease at the Beginning of Maintenance Therapy Indicates Poor Outcome in Children With T-Cell Acute Lymphoblastic Leukemia

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 1226-1232 ◽  
Author(s):  
Salvatore P. Dibenedetto ◽  
Luca Lo Nigro ◽  
Sharon Pine Mayer ◽  
Giovanni Rovera ◽  
Gino Schilirò
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Maintenance Therapy ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Strong Predictor ◽  
Blot Hybridization ◽  
Cell Receptor ◽  
Dot Blot ◽  
Poor Outcome

Abstract The aims of this study were twofold: (1) to assess the marrow of patients with T-lineage acute lymphoblastic leukemia (T-ALL) for the presence of molecular residual disease (MRD) at different times after diagnosis and determine its value as a prognostic indicator; and (2) to compare the sensitivity, rapidity, and reliability of two methods for routine clinical detection of rearranged T-cell receptor (TCR). Marrow aspirates from 23 patients with T-ALL diagnosed consecutively from 1982 to 1994 at the Division of Pediatric Hematology and Oncology, University of Catania, Italy, were obtained at diagnosis, at the end of induction therapy (6 to 7 weeks after diagnosis), at consolidation and/or reinforced reinduction (12 to 15 weeks after diagnosis), at the beginning of maintenance therapy (34 to 40 weeks after diagnosis), and at the end of therapy (96 to 104 weeks after diagnosis). DNA from the patients' marrow was screened using the polymerase chain reaction (PCR) for the four most common TCR δ rearrangements in T-ALL (Vδ1Jδ1, Vδ2Jδ1, Vδ3Jδ1, and Dδ2Jδ1) and, when negative, further tested for the presence of other possible TCR δ and TCR γ rearrangements. After identification of junctional rearrangements involving V, D, and J segments by DNA sequencing, clone-specific oligonucleotide probes 5′ end-labeled either with fluorescein or with [γ-32P]ATP were used for heminested PCR or dot hybridization of PCR products of marrows from patients in clinical remission. For 17 patients with samples that were informative at the molecular level, the estimated relapse-free survival (RFS) at 5 years was 48.6% (±12%). The sensitivity and specificity for detection of MRD relating to the outcome were 100% and 88.9% for the heminested fluorescence PCR and 71.4% and 88.9% for Southern/dot blot hybridization, respectively. Predictive negative and positive values were 100% and 90.7% for heminested fluorescence PCR, respectively. The probability of RFS based on evidence of MRD as detected by heminested fluorescence PCR at the time of initiation of maintenance therapy was 100% and 0% for MRD-negative and MRD-positive patients, respectively. Thus, the presence of MRD at the beginning of maintenance therapy is a strong predictor of poor outcome, and the molecular detection of MRD at that time might represent the basis for a therapeutic decision about such patients. By contrast, the absence of MRD at any time after initiation of treatment strongly correlates with a favorable outcome. The heminested fluorescence PCR appears to be more accurate and more rapid than other previously used methods for the detection of residual leukemia.

scholarly journals TP53mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens

Cancer ◽  
2017 ◽  
Vol 123 (19) ◽  
pp. 3717-3724 ◽  
Author(s):  
Rashmi Kanagal-Shamanna ◽  
Preetesh Jain ◽  
Koichi Takahashi ◽  
Nicholas J. Short ◽  
Guilin Tang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Poor Outcome

CD9 expression indicates a poor outcome in acute lymphoblastic leukemia

2018 ◽  
Vol 21 (4) ◽  
pp. 781-786 ◽  
Author(s):  
Peiqi Liang ◽  
Miao Miao ◽  
Zhuogang Liu ◽  
Hongtao Wang ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Outcome

Acute Lymphoblastic Leukemia (ALL) With Low-Hypodiploid/Near-Triploid Karyotype Is a Specific Clinical Entity Characterized By a High TP53 Mutation Frequency

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 615-615
Author(s):  
Verena Patterer ◽  
Melanie Zenger ◽  
Susanne Schnittger ◽  
Sandra Weissmann ◽  
Franziska Poetzinger ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chromosome Number ◽  
Mutation Frequency ◽  
Tp53 Mutation ◽  
Lymphoblastic Leukemia ◽  
Chromosome 17 ◽  
Typical Pattern ◽  
Employment Equity ◽  
Poor Outcome ◽  
Equity Ownership

Abstract Background B-lineage acute lymphoblastic leukemia (ALL) called B lymphoblastic leukemia/lymphoma by the WHO classification 2008 is subdivided into 5 subgroups defined by a specific translocation (t(9;22)(q34;q11); t(v;11q23); t(12;21)(p13;q22); t(5;14)(q31;q32); t(1;19)(q23;p13.1)). Two additional categories are defined on the basis of chromosome number: ALL with hyperdiploidy and hypodiploid ALL. The former group comprises a well defined genetic subset with blasts containing >50 and usually >66 chromosomes. In contrast, the hypodiploid subgroup is very heterogeneous and comprises ALL with a chromosome number of >46 chromosomes to near-haploid. Aim To characterize this rare subset of ALL with low hypodiploidy in detail with respect to cytogenetic abnormalities, molecular mutations and clinical outcome. Patients and Methods Out of a total cohort of 878 ALL patients analyzed between 2005 and 2013 we selected a subset of 26 cases harbouring a hypodiploid clone with 1) a chromosome number of ≤40 or 2) a near triploid clone with 56-78 chromosomes that had arisen from a low hypodiploid clone by duplication of the chromosome set. Data on karyotype, array CGH and FISH for rearrangement of BCR-ABL1, ETV6 and MLL was available in all cases. Further, cases were investigated for mutations in NRAS, KRAS, TP53, NOTCH1, FBXW7 and intragenic deletions of IKZF1. For 17 cases data on the immunophenotype was available. Clinical follow-up data was available for 19 pts. Results 12/17 pts showed a common B ALL-phenotype, 5 pts were classified as Pro-B-ALL. All cases were negative for t(12;21)(p13;q22)/ETV6-RUNX1, t(9;22)(q34;q11)/BCR-ABL1 and translocations involving the MLL gene. The pattern of chromosomal losses was non-random. One chromosome 3 and 7 was lost in all 26 cases. Other frequently deleted chromosomes were chromosomes 15 (n=24), 17 (n=25), 13, 16 (lost in 23 cases each), 9 (n=18), 4 (n=17), 12 and 20 (lost in 16 cases each), which were all deleted in more than 50% of the cases, confirming a very specific pattern of chromosome losses. Less frequently lost were chromosomes 2 (n=12), 8 (n=11), 14 (n=10), 5 (n=8) and 18 (n=7). Rarely lost were chromosomes 6, 11 (lost in 5 cases each), 1, 10, 19, 22 (lost in 4 cases each) and the sex chromosomes X or Y in 3 cases each. Only chromosome 21 was retained in all cases. In 14 cases with doubling of the low-hypodiploid karyotype we observed the same typical pattern of gains and losses with two copies of typically lost chromosomes and four copies of typically retained chromosomes. In 11/14 pts we detected additional losses of chromosomes resulting in trisomies, most frequently of chromosomes 2 (n=7), 5 and 14 (n=6), respectively. Structural abnormalities in addition to chromosome losses were found in 85% of pts by chromosome banding analysis, none of these was recurrent. The only recurrent submicroscopic deletion detected by aCGH was a 9p deletion encompassing the CDKN2A/B locus (n=7), which was homozygous in 4 pts. As 14 additional pts showed a monosomy 9, only 5 pts did not show a deletion of at least one CDKN2A/B copy. We discovered no mutations in FBXW7, NOTCH1 and KRAS and only one mutation in NRAS. Further, no intragenic deletion of IKZF1 was detected. However, and most interestingly, 24 out of 26 pts (92.3%) showed a mutation within the TP53 gene. In 23/24 pts with TP53 mutation and in both pts with TP53wt chromosome 17 was monosomic. Further, both patients with TP53wt and monosomy 17 showed a remarkably low chromosome number of 25 and 28 chromosomes compared to TP53mut pts who showed at least 32 chromosomes. Outcome was poor: 2-year-overall survival rate of pts treated with intensive chemotherapy (n=19) was only 20%. Conclusions ALL with low hypodiploidy is characterized by a typical pattern of chromosome losses including loss of chromosomes 7, 3, 15, 17, 13 and 16, a very high TP53 mutation frequency and poor outcome. A duplication of the low-hypodiploid karyotype occurs frequently and results in a near triploid karyotype based on the definition by merely counting chromosomes but in fact is a very low tetraploid chromosome set. Our data suggests the introduction of a novel WHO entity within the B lymphoblastic leukaemia/lymphoma group showing low-hypodiploid/very low-tetraploid karyotype and concomitant TP53 mutation. The poor outcome of this specific ALL subset might be related to the high TP53 mutation frequency in combination with loss of the second TP53 allele due to monosomy 17. Disclosures: Patterer: MLL Munich Leukemia Laboratory: Employment. Zenger:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Weissmann:MLL Munich Leukemia Laboratory: Employment. Poetzinger:MLL Munich Leukemia Laboratory: Employment. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Bellos:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

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