Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia

Very rare cases of human T cell acute lymphocytic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that quite 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 within the molecular pathogenesis of human T-ALL and supply a robust rationale for targeted therapies that interfere with NOTCH signaling. [1]

Antisera to acute lymphoblastic leukemia cells

Antisera to acute lymphocytic leukemia cells are raised in rabbits by injecting ALL cells coated in vitro with rabbit antibodies directed against normal lymphocyte antigens. The resultant antisera were absorbed with various normal tissues and tested by immunofluorescence for his or her ability to discriminate between ALL and other leukemias, and between ALL and normal cells. Fourteen out of 19 ALL patients at presentation had circulating cells reactive with the antisera. Three of those had a bone marrow diagnosis of ALL with no apparent abnormal cells within the peripheral blood. Of the five unreactive cases, three were the sole T cell-like leukemias within the ALL group. Several patients considered to be in complete hematological remission had alittle number of anti-ALL binding cells in their blood. [2]

Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia

BACKGROUND: Despite best current therapy, up to twenty of pediatric patients with acute lymphocytic leukemia (ALL) have a relapse. Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities altogether , but the prognostic implications of those abnormalities haven’t been defined.

METHODS: We studied a cohort of 221 children with high-risk B-cell–progenitor ALL with the utilization of single-nucleotide–polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis. Children with known very-high-risk ALL subtypes (i.e., BCR-ABL1–positive ALL, hypodiploid ALL, and every one in infants) were excluded from this cohort. A copy-number abnormality was identified as a predictor of poor outcome, and it had been then tested in an independent validation cohort of 258 patients with B-cell–progenitor ALL. [3]

Comprehensive profiling of disease-relevant copy number aberrations for advanced clinical diagnostics of pediatric acute lymphoblastic leukemia

Acute lymphocytic leukemia is that the commonest pediatric cancer characterized by a heterogeneous genomic landscape with copy number aberrations occurring at various stages of pathogenesis, disease progression, and treatment resistance. during this study, disease-relevant copy number aberrations were profiled in bone marrow samples of 91 children with B- or T-cell precursor acute lymphocytic leukemia using digital multiplex ligation-dependent probe amplification (digitalMLPATM). Whole chromosome gains and losses, subchromosomal copy number aberrations, also as unbalanced alterations conferring intrachromosomal gene fusions were simultaneously identified with results available within 36 hours. [4]

The Expression Patterns of APC2 and APC7 in Newly Diagnosed Acute Lymphoblastic Leukemia

Acute lymphocytic leukemia (ALL) may be a heterogeneous sort of disease that’s currently categorized supported cell morphology, immunophenotype, genetic abnormalities and organic phenomenon pattern. Although these classifications are valuable within the determination of patient’s survival and treatment intensity, the response of patients to treatment and subsequently their survival are highly different, even in each subtype. So checking out new molecules involved within the leukemogenesis, disease progression, treatment resistance or candidate targets for therapy are critically sensed. APC/C may be a multi-subunit E3 ligase that has essential role in metaphase progression and seems to be essentially involved in tumorgenesis and cancer progression. We analyzed the expression of APC2 and APC7 gene as two key subunits of this complex in 57 newly diagnosed ALL patients with quantitative RT-PCR. APC2 and APC7 were significantly over-expressed in 33 (57.9%) and 38 (66.7%) of patients respectively (P value of 0.014 and 0.009) using two-tailed Student’s t tests. [5]


[1] Weng, A.P., Ferrando, A.A., Lee, W., Morris, J.P., Silverman, L.B., Sanchez-Irizarry, C., Blacklow, S.C., Look, A.T. and Aster, J.C., 2004. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science, 306(5694), (Web Link)

[2] Greaves, M.F., Brown, G., Rapson, N.T. and Lister, T.A., 1975. Antisera to acute lymphoblastic leukemia cells. Clinical immunology and immunopathology, 4(1), (Web Link)

[3] Mullighan, C.G., Su, X., Zhang, J., Radtke, I., Phillips, L.A., Miller, C.B., Ma, J., Liu, W., Cheng, C., Schulman, B.A. and Harvey, R.C., 2009. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. New England Journal of Medicine, 360(5), (Web Link)

[4] Comprehensive profiling of disease-relevant copy number aberrations for advanced clinical diagnostics of pediatric acute lymphoblastic leukemia
Richárd Kiss, Ambrus Gángó, Anne Benard-Slagter, Bálint Egyed, Irén Haltrich, Lajos Hegyi, Karel de Groot, Péter Attila Király, Szilvia Krizsán, Béla Kajtár, Henriett Pikó, László Pajor, Ágnes Vojcek, András Matolcsy, Gábor Kovács, Károly Szuhai, Suvi Savola, Csaba Bödör & Donát Alpár
Modern Pathology (2019) (Web Link)

[5] Khosravi Farsani, M. R., Amiri‏., Hajifathali, A., Mohammadi, M., Jabari, M., Farsani, M. A. and Asadi-Samani, M. (2017) “The Expression Patterns of APC2 and APC7 in Newly Diagnosed Acute Lymphoblastic Leukemia”, Journal of Pharmaceutical Research International, 19(3), (Web Link)

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