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(Created page with " <div style="background-color: #E0EEEE; {{round corners}} padding: 2em 2em; margin-right: 5px;"> *The principle diagnostic value of CD38 is that its expression is retained and generally increased during differentiation to plasma cells *CD38 expression has some value in predicting prognosis in CLL *CD38 is also expressed by committed stem cells together with CD34 and can occasionally be of value in acute leukaemia diagnosis </div> <span style="color:navy">'''Norma...")
 
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*The principle diagnostic value of CD38 is that its expression is retained and generally increased during differentiation to plasma cells
:<span style="color:navy">'''Summary'''</span>
*CD38 expression has some value in predicting prognosis in CLL
*CD38 is also expressed by committed stem cells together with CD34 and can occasionally be of value in acute leukaemia diagnosis


:A useful marker of myeloid lineage although expression depends significantly on stage and type of maturation (see Diagnostic Role). CD13 has recognised aberrant expression in some cases of ALL (particularly B-lineage)


</div>
</div>


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<span style="color:navy">'''Normal expression and function'''</span>
<span style="color:navy">'''Normal expression and function'''</span>


CD13 is an enzyme which cleaves eutral amino acids from the N terminus of small peptides. The function of CD13 appears to vary with the tissue and the precise function in myeloid cells is unclear.  The pattern of expression that is similar to other pan-myeloid markers (CD117 and CD33), but with levels generally increasing during maturation (contrasting with CD33 whose expression decreases). Maturation of myeloid cells may be partly identified through the relative CD33/13 expression.
CD13 is a cell surface enzyme whose function varies between tissues; its precise function in myeloid cells is unclear.  The pattern of expression is similar to other pan-myeloid markers (CD117 and CD33), but with levels generally increasing during maturation (contrasting with CD117 and CD33 whose expression decreases). Maturation of normal myeloid cells may therefore be partly idicated through the relative CD33/13 expression.




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<span style="color:navy">'''Diagnostic role'''</span>  
<span style="color:navy">'''Diagnostic role'''</span>  


*Together with other markers (CD117, CD33 and MPO) CD13 identifies myeloid lineage, particularly acute myeloid leukaemia. CD13 is also found on myelomonocytic and monocytic leukaemias.
*Together with other markers (CD117, CD33 and MPO), CD13 can be used to identify myeloid lineage in acute myeloid leukaemia.  


*Expression is often absent on more primitive AML, erythroid or megakaryoblastic AML
*CD13 is also expressed by myelomonocytic and monocytic leukaemia cells where a high ratio of CD13/CD33 may help suggest monocytic lineage


*Aberrant expression by ALL occurs in around 30% of patients (at the 20% threshold)
*Expression of CD34 is not required to diagnose AML and is not fully specific - CD13 is often absent on more primitive AML cases as well as on those with erythroid or megakaryoblastic differentiation; while aberrant expression in ALL is recognised to occur in around 30% of patients.
 
CD13 is often regarded as less specific for myeloid lineage than either CD117 or MPO.
*Overall high sensitivity, but may be less specific than CD117 or MPO.
   
   


<span style="color:navy">'''Other relevant information:'''</span>  
<span style="color:navy">'''Other relevant information:'''</span>  


 
Expression is not restricted to myeloid cells, and CD13 is particularly expressed on small intestinal and renal tubular epithelial cells and synaptic membranes from the CNS.
Outside the haematopoietic system CD13 is particularly expressed on small intestinal and renal tubular epithelial cells and synaptic membranes from the CNS.




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Expression by acute leukaemias and by haematogones
{| class=wikitable style="text-align: center; font-size:80%; width: 100%; height 20px;"
|-
!colspan="8"|'''Expression in primitive cell types'''</font>
|- <span style="font-size:70%">
!AML!!CMML !!B ALL !!BL ||T ALL !!ETP ALL !!MPAL ||Hgn</span>
|-<span style="font-size:70%">
|style="width: 12.5%; background: #004466; color:white"|80-100%*
|style="width: 12.5%; background: #004466; color:white"|80-100%
|style="width: 12.5%; background: #00b8e6; color:black"|20-40%**
|style="width: 12.5%; background: #66e0ff; color:black"|5-20%
|style="width: 12.5%; background: #66e0ff; color:black"|5-20%
|style="width: 12.5%; background: #00b8e6; color:black"|20-40%**
|style="width: 12.5%; background: #00b8e6; color:black"|20-40%**
|style="width: 12.5%; background:#004466; color:white"|80-100%***
|-
|}


<gallery widths="40px" heights="40px" >
File:Poss.png|''Pro-B ALL''|link=Flow cytometry key
File:Poss.png|''Early pre-B ALL''|link=Flow cytometry key
File:Poss.png|''Pre-B ALL''|link=Flow cytometry key
File:Rare.png|''B ALL''|link=Flow cytometry key
File:Rare.png|''Pro-T ALL''|link=Flow cytometry key
File:Rare.png|''Mature-T ALL''|link=Flow cytometry key
File:Hi.png|''AML''|link=Flow cytometry key
File:Freq.png|''Haemato-gones''|link=Flow cytometry key
</gallery>


<span style="font-size:90%">'''Notes'''
<span style="font-size:90%">'''Notes:''' The main application is in AML. Aberrant expression is seen particularly in B-lineage, although it may be less likely in Burkitt lymphoma. CD13 is not generally expressed in T-ALL. CD13 expression can indicate MPAL or ETP-ALL if other markers suggest this.


''In ALL the expression of CD13 is more likely in B-ALL but is also seen in T-ALL''


''In AML CD13 is expressed in around 80% of cases''
{| class=wikitable style="text-align: center; font-size:80%; width: 100%; height 20px;"
 
|-
''In haematogones expression of CD13 is very frequent''
!colspan="8"|'''Expression in mature B cell neoplasms'''
</span>
|- <span style="font-size:70%">
! CLL !! MCL !!FL!! MZL !! HCL !! DLBCL || LPL !! PCL
|-<span style="font-size:70%">
|style="width: 12.5%; background: #E6FAFF; color:black"|<5%
|style="width: 12.5%; background: #E6FAFF; color:black"|<5%
|style="width: 12.5%; background: #E6FAFF; color:black"|<5%
|style="width: 12.5%; background: #E6FAFF; color:black"|<5%
|style="width: 12.5%; background: #E6FAFF; color:black"|<5%
|style="width: 12.5%; background: #E6FAFF; color:black"|<5%
|style="width: 12.5%; background: #00b8e6; color:black"|20-40%
|style="width: 12.5%; background: #00b8e6; color:black"|20-40%
|-
|}


<span style="font-size:90%">'''Notes:''' overall expression is uncommon in mature B-lymphoproliferative disorders, but may occur at plasma cell differentiation</span>


Expression by B-lymphoproliferative disorders
<span style="font-size:90%"> Additional note [[PLL]] and [[vHCL]] are no longer included, click on the name for further information</span>


<gallery widths="40px" heights="40px" >
File:Rare.png|frame|''CLL''|link=Flow cytometry key
File:Rare.png|''PLL''|link=Flow cytometry key
File:Rare.png|''MCL''|link=Flow cytometry key
File:Rare.png|''FL'|link=Flow cytometry key
File:Rare.png|''HCL''|link=Flow cytometry key
File:Rare.png|''HCLv''|link=Flow cytometry key
File:Rare.png|''MZL''|link=Flow cytometry key
File:Rare.png|''LPL''|link=Flow cytometry key
File:Rare.png|''PCs''|link=Flow cytometry key
</gallery>




 
{| class=wikitable style="text-align: center; font-size:80%; width: 62.4%; height 40px;"
 
 
----
 
'''KEY'''
 
 
<div class="toccolours mw-collapsible mw-collapsed" style="font-size 80%; overflow:auto;">
 
The indicated expression frequency, indicates the approximate frequency of occurrence in each particular disease type.
 
 
[[File:Rare.png|30px|link=]]
 
rare (<5%)
 
[[File:Poss.png|30px|link=]]
 
possible (5-20%)
 
[[File:Mod.png|30px|link=]]
 
likely (20-40%)
 
[[File:Freq.png|30px|link=]]
 
frequent (40-80%)
 
[[File:Hi.png|30px|link=]]
 
expected (>80%)
 
 
Where expression level is unusual or characteristic of a disorder this is indicated by text:
 
 
</div>
 
 
 
 
----
 
 
 
<span style="color:navy">'''''DETAILS'''''</span>
 
CD38 helps initiate the mobilsation of intracellular calcium, activating a wide array of cell functions that depend on cell type. In haematological cell types CD38 is widely expressed by lymphoid cells and by particular myeloid cells – often in a stage-specific manner. For B lymphocytes CD38 expression is acquired as stem cells commit to B-cell lineage, then lost as mature B cells emerge from bone marrow before being re-acquired by germinal center cells and at the time of plasma cell differentiation. It is also expressed by NK cells and by activated T lymphocytes. CD38 is expressed by most early precursor cells, and by mature monocytes and granulocytes.
 
 
<span style="color:navy">'''What is its diagnostic role?'''</span>
 
The major value lies in its use together with CD138, (possibly also CD45 and light-scatter) to identify plasma cells. This may be valuable for diagnosis or monitoring of myeloma. However, CD38 is expressed by both normal and myelomatous plasma cells, and expression may be dimmer on neoplastic plasma cells. Significant CD38 expression (expression by more than 20% of cells) has been shown to predict poor outcome in chronic lymphocytic leukaemia. CD38 is commonly expressed on blasts of any lineage and therefore provides little diagnostic distinction.
 
 
<span style="color:navy">'''Other relevant information:'''</span> CD38 is a therapeutic target, daratumumab is a monoclonal antibody which binds to CD38 and is used in the treatment of myeloma.
 
 
----
 
<span style="color:navy">'''''SUMMARY TABLES'''''</span>
 
{| class=wikitable style="text-align: center; width: 800px;"
 
|-
|-
!colspan="8"|Expression of CD38 by primitive lymphoid cells: ALL and haematogones
!colspan="7"|'''CD13 expression: mature T cell neoplasms'''
|-  
|-  
! pro-B ALL !! early pre-B ALL !!pre-B ALL!! B-ALL !!pro-T ALL !!mature-T ALL !!AML !!Haematogones
! ATLL !! CTCL Sezary !! T-PLL !! T-LGL !! NK-LGL
|-
|-
|style= "width: 100px; height: 20px; background: #006699; color:white"|
|style= "width: 20%; background: #FFE4E1; color:black"|limited
|style="width: 100px; background: #006699; color:white"|
|style="width: 20%; background: #FFE4E1; color:black"|limited
|style="width: 100px; background: #006699; color:white"|
|style="width: 20%; background: #FFE4E1; color:black"|limited
|style="width: 100px; background: #006699; color:white"|
|style= "width: 20%; background: #FFE4E1; color:black"|limited
|style="width: 100px; background: #006699; color:black"|
|style="width: 20%; background: #FFE4E1; color:black"|limited
|style="width: 100px; background: #006699; color:black"|
|style="width: 100px; background: #00b8e6; color:white"|*
|style="width: 100px; background: #004466; color:white"|stg
|-
|-
|}
|}
<span style="font-size:80%">''* low expression correlates with subtype e.g. APML''</span>


{| class=wikitable style="text-align: center; width: 800px; height 20px;"
<span style="font-size:90%">'''Notes:''' There is limited published evidence, but reports suggest expression of CD13 is uncommon in mature T cell malignancy</span>
 
|-
!colspan="8"|Expression of CD38 by mature B cells: B-lymphoproliferative disorders
|-
! CLL !! MCL !!FL!! HCL !!HCv !!MZL!!LPL!!PCL
|-
|style= "width: 100px; background: #00b8e6; color:black"|*
|style="width: 100px; background: #004466; color:white"|
|style="width: 100px; background: #004466; color:white"|**
|style= "width: 100px; background: #00b8e6; color:white"|
|style= "width: 100px; background: #00b8e6; color:white"|
|style="width: 100px; background: #004466; color:white"|
|style="width: 100px; background: #006699; color:white"|
|style="width: 100px; background: #004466; color:white"|stg/mod
|-
|}
<span style="font-size:80%">''*May indicate adverse prognostic when present on more than 20% of cells''</span>
 
<span style="font-size:80%">''**May be weak''</span>


----
----
<span style="font-size:80%">'''''1. Colour key:''''' ''- the likelihood of any individual case expressing this marker, indicated by colour:''
</span>
{| class=wikitable style="text-align: center; font-size:80%; width: 600px; height: 20px;
|-
|style= "background: #E6FAFF; |Rare (<5%)
|style="background: #66e0ff;"|Possible (5-20%)
|style="background: #00b8e6;"|Likely (20-40%)
|style="background: #006699; color:white"|Frequent (40-80%)
|style="background: #004466; color:white"|Expected (80-100%)
|-
|}
<span style="font-size:80%">
'''''2. Text key''''': - ''where expression level is characteristic of a disorder this is indicated by text:''
</span>
<span style="font-size:80%">
'''abs''' = absent expression, '''wk''' = weak expression, '''mod''' = moderate expression, '''stg''' = strong expression, '''sub''' = expression may be on a sub-population of cells''
</span>

Latest revision as of 21:37, 4 July 2023


Summary
A useful marker of myeloid lineage although expression depends significantly on stage and type of maturation (see Diagnostic Role). CD13 has recognised aberrant expression in some cases of ALL (particularly B-lineage)



Normal expression and function

CD13 is a cell surface enzyme whose function varies between tissues; its precise function in myeloid cells is unclear. The pattern of expression is similar to other pan-myeloid markers (CD117 and CD33), but with levels generally increasing during maturation (contrasting with CD117 and CD33 whose expression decreases). Maturation of normal myeloid cells may therefore be partly idicated through the relative CD33/13 expression.


Diagnostic role

  • Together with other markers (CD117, CD33 and MPO), CD13 can be used to identify myeloid lineage in acute myeloid leukaemia.
  • CD13 is also expressed by myelomonocytic and monocytic leukaemia cells where a high ratio of CD13/CD33 may help suggest monocytic lineage
  • Expression of CD34 is not required to diagnose AML and is not fully specific - CD13 is often absent on more primitive AML cases as well as on those with erythroid or megakaryoblastic differentiation; while aberrant expression in ALL is recognised to occur in around 30% of patients.

CD13 is often regarded as less specific for myeloid lineage than either CD117 or MPO.


Other relevant information:

Expression is not restricted to myeloid cells, and CD13 is particularly expressed on small intestinal and renal tubular epithelial cells and synaptic membranes from the CNS.



SUMMARY TABLES


Expression in primitive cell types
AML CMML B ALL BL T ALL ETP ALL MPAL Hgn
80-100%* 80-100% 20-40%** 5-20% 5-20% 20-40%** 20-40%** 80-100%***


Notes: The main application is in AML. Aberrant expression is seen particularly in B-lineage, although it may be less likely in Burkitt lymphoma. CD13 is not generally expressed in T-ALL. CD13 expression can indicate MPAL or ETP-ALL if other markers suggest this.


Expression in mature B cell neoplasms
CLL MCL FL MZL HCL DLBCL LPL PCL
<5% <5% <5% <5% <5% <5% 20-40% 20-40%

Notes: overall expression is uncommon in mature B-lymphoproliferative disorders, but may occur at plasma cell differentiation

Additional note PLL and vHCL are no longer included, click on the name for further information


CD13 expression: mature T cell neoplasms
ATLL CTCL Sezary T-PLL T-LGL NK-LGL
limited limited limited limited limited

Notes: There is limited published evidence, but reports suggest expression of CD13 is uncommon in mature T cell malignancy