Top ▲

Acute lymphocytic leukemia (ALL)

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

✖
Disease ID:1172
Name:Acute lymphocytic leukemia (ALL)
Associated with:3 targets
2 immuno-relevant targets
2 immuno-relevant ligands
Synonyms
Acute lymphoblastic leukemia
Description
ALL is a subtype of acute leukemia
Database Links
OMIM: 613065

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

✖
Key to terms and symbols
CD3e
Comments:  CD3e is the molecular target of approved drug blinatumomab, as a treatment Philadelphia chromosome-negative precursor B-cell ALL
Ligand interactions: 
Ligand Comments
blinatumomab
Approved specifically for Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL.
CD19
Comments:  CD19 is one of the molecular targets of the bi-specific antibody drug blinatumomab (also binds CD3e).
Ligand interactions: 
Ligand Comments
blinatumomab
Approved specifically for Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL.
regulator of G-protein signaling 1
References:  2

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

✖
Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
inotuzumab ozogamicin
Immuno Disease Comments: Approved therapy for ALL.
Clinical Use: The EMA has granted inotuzumab ozogamicin orphan designation for the treatment of the rare disease B-cell acute lymphoblastic leukemia (ALL).
Although Phase 3 clinical trials assessing inotuzumab ozogamicin as a treatment for non-Hodgkin lymphoma have been terminated (NCT01232556 and NCT00562965) because they were unlikely to meet their primary objective of improving overall survival (OS), a separate Phase 3 trial in patients with ALL is ongoing (NCT01564784). Preliminary results from this ALL trial indicated extended progression-free and overall survival with inotuzumab ozogamicin compared to standard therapy [3]. The FDA granted breakthrough therapy designation for inotuzumab ozogamicin for ALL based on these results. The EMA had granted orphan designation for ALL in 2013. Both the EMA and FDA converted to full approval as a treatment for ALL in 2017. Veno-occlusive liver disease was observed as a major adverse event associated with inotuzumab ozogamicin therapy.
In March 2024 FDA approval was expanded to include treatment of relapsed/refractory CD22-positive B-cell precursor ALL in paediatric patients (>1 yr old). | View clinical data
blinatumomab
Immuno Disease Comments: Approved specifically for Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL.
Clinical Use: In December 2014 the FDA approved blinatumomab for use in the treatment of Philadelphia chromosome-negative (Ph-) precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL. Full approval for use in the European Union (to treat Ph- relapsed/refractory B-precursor ALL) was granted in November 2015, subsequent to orphan drug designation since mid 2014.
In July 2017, the FDA expanded approval to include treatment of relapsed/refractory B-cell precursor ALL in adults and children, based on data from the Phase 3 TOWER study that shows that blinatumomab single agent therapy exhibits superior improvement in median overall survival over standard of care chemotherapy. This is the first single-agent immunotherapy approved to treat patients with Ph- relapsed or refractory B-cell precursor ALL. March 2018 saw FDA approval expanded further to include treatment of adult and pediatric patients with B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD), based on the BLAST trial (NCT01207388) [1].

Blinatumomab is undergoing clinical trial for other forms of ALL and lymphoma. A list of current trials can be viewed at ClinicalTrials.gov. | View clinical data
Bioactivity Comments: The development of blinatumomab is covered by patent US7635472 [4], based on peptide sequence matches of the two antigen-binding variable heavy chains regions of blinatumomab. In this patent specificity and efficacy of blinatumomab binding was determined by FACS analysis and ELISA. However, the specific clone producing blinatumomab is not reported, nor are binding affinity values for antibody-antigen interactions | View biological activity

References

Show »

1. Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Brüggemann M, Horst HA et al.. (2018) Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood, 131 (14): 1522-1531. [PMID:29358182]

2. Hong JX, Wilson GL, Fox CH, Kehrl JH. (1993) Isolation and characterization of a novel B cell activation gene. J Immunol, 150 (9): 3895-904. [PMID:8473738]

3. Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gökbuget N, O'Brien S, Wang K, Wang T et al.. (2016) Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med, 375 (8): 740-53. [PMID:27292104]

4. Kufer P, Lutterbuse R, Kohleisen B, Zeman S, Bauerle P. (2009) Single chain antibody construct comprising binding domains specific for human CD3 and human CD19. Patent number: US7635472. Assignee: Micromet Ag. Priority date: 31/05/2003. Publication date: 22/12/2009.