Molecule Information

General Information of the Molecule (ID: Mol01824)

• Name: B-cell receptor CD22 (CD22) ,Homo sapiens
• Synonyms: B-lymphocyte cell adhesion molecule; BL-CAM; Sialic acid-binding Ig-like lectin 2; Siglec-2; T-cell surface antigen Leu-14; CD antigen CD22
• Molecule Type: Protein
• Gene Name: CD22
• Gene ID: 933
• Location: chr19:35,319,261-35,347,361[+]
• Sequence:
  MHLLGPWLLLLVLEYLAFSDSSKWVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFH
  NPEYNKNTSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCTLSIHPVHLNDSGQLGLR
  MESKTEKWMERIHLNVSERPFPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEG
  VPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNVKH
  TPKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVT
  KDQSGKYCCQVSNDVGPGRSEEVFLQVQYAPEPSTVQILHSPAVEGSQVEFLCMSLANPL
  PTNYTWYHNGKEMQGRTEEKVHIPKILPWHAGTYSCVAENILGTGQRGPGAELDVQYPPK
  KVTTVIQNPMPIREGDTVTLSCNYNSSNPSVTRYEWKPHGAWEEPSLGVLKIQNVGWDNT
  TIACAACNSWCSWASPVALNVQYAPRDVRVRKIKPLSEIHSGNSVSLQCDFSSSHPKEVQ
  FFWEKNGRLLGKESQLNFDSISPEDAGSYSCWVNNSIGQTASKAWTLEVLYAPRRLRVSM
  SPGDQVMEGKSATLTCESDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQ
  GTNSVGKGRSPLSTLTVYYSPETIGRRVAVGLGSCLAILILAICGLKLQRRWKRTQSQQG
  LQENSSGQSFFVRNKKVRRAPLSEGPHSLGCYNPMMEDGISYTTLRFPEMNIPRTGDAES
  SEMQRPPPDCDDTVTYSALHKRQVGDYENVIPDFPEDEGIHYSELIQFGVGERPQAQENV
  DYVILKH
• Function: Mediates B-cell B-cell interactions. May be involved in the localization of B-cells in lymphoid tissues. Binds sialylated glycoproteins; one of which is CD45. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site can be masked by cis interactions with sialic acids on the same cell surface. Upon ligand induced tyrosine phosphorylation in the immune response seems to be involved in regulation of B-cell antigen receptor signaling. Plays a role in positive regulation through interaction with Src family tyrosine kinases and may also act as an inhibitory receptor by recruiting cytoplasmic phosphatases via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules.
• Uniprot ID: CD22_HUMAN
• Ensembl ID: ENSG00000012124
• HGNC ID: HGNC:1643

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Inotuzumab ozogamicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Relapsed B-acute Lymphoblastic leukaemia [1]

• Resistant Disease: Relapsed B-acute Lymphoblastic leukaemia [ICD-11: 2B33.3]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: Enzyme-linked immunosorbent assay (ELISA)
• Mechanism Description: One important escape mechanism at relapse may be modulation of the CD22 antigen expression on leukemic blasts, analogous to antigen loss associated with CD19-directed therapies such as blinatumomab and CD19-CAR T-cell therapies.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Relapsed B-acute Lymphoblastic leukaemia [2]

• Resistant Disease: Relapsed B-acute Lymphoblastic leukaemia [ICD-11: 2B33.3]
• Resistant Drug: Inotuzumab ozogamicin
• Molecule Alteration: Missense mutation; p.V238 frameshift
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Experiment for Molecule Alteration: Whole genome sequencing assay; Whole transcriptome RNA-sequencing assay
• Experiment for Drug Resistance: Bone marrow biopsy assay; Flow cytometry assay
• Mechanism Description: Decreased surface CD22 expression and receptor density have been reported as mechanisms of acquired@resistance to InO and CD22 CAR-T in some patients relapsing with B-lineage acute leukaemia. Truncating CD22 mutation with concomitant loss of the receptor from the cell surface represents a new mechanism of leukaemic cell escape

References

• Ref 1: LincHOTAIR epigenetically silences miR34a by binding to PRC2 to promote the epithelial-to-mesenchymal transition in human gastric cancer Cell Death Dis. 2015 Jul 2;6(7):e1802. doi: 10.1038/cddis.2015.150.
• Ref 2: Inotuzumab ozogamicin resistance associated with a novel CD22 truncating mutation in a case of B-acute lymphoblastic leukaemiaBr J Haematol. 2020 Oct;191(1):123-126. doi: 10.1111/bjh.16949. Epub 2020 Jul 9.