Re: A CD45RO M1 Leukemia?

From: Rafael Nunez (rafaeln@vetvir.unizh.ch)
Date: Fri Jan 16 1998 - 12:07:35 EST


Maryalice
Lets get back to the drawing table and try to make sense with this case.
CD19 and CD20 are B cell markers, is this a B cell leukemia? may be but B
cell leukemia without kappa and lambda, should be a PreB cell or even
early. (see papers from Fritz Meltchers (Basel) and Max Cooper Birmingham
AL). Since it is CD10+, it sounds good and fit with the HLA-DR+(see seminal
papers from Henry Kunkel and Bob Winchester), Maryalice, you made the point.
CD34 is a stem cell marker, so is this a stem cell leukemia? may be and
everybody is happy.
But "Houston we have a problem" because CD13 (Aminopeptidase) and CD33 are
markers of monocyte lineage. Then lets found a win-win solution. A leukemia
with both phenotypes, early, early B and myeloid.  However, is raining in
the party since CD45RO is associated with memory T cell, are this memory T
cells?,  is unlike. Then, lets digging in the library and MEDline, and
after 13412  references of CD45, there is a nice description of 4 cases of
M1 CD45RO and they said that is a unique situation. But still there is a
problem, is a publication in Japanese with abstract in English and I could
not get the full text. (93353742- Tatsumi E, Yoneda N, Kawano S, Yamaguchi
N, Department of Laboratory Medicine, Kobe University School of Medicine.
TI  - [Cytokine in phenotypic analysis of leukemia/lymphoma: suppression
      of gene expression of myeloperoxidase by IFN-gamma and subset of AML
      M1 defined by CD45RO+/RA-, CD7(-), CD34(-) and non-inducible HLA-DR
      antigen]. [Japanese]
SO  - Rinsho Byori 1993 Apr;41(4):377-83) but Chang could get it easily in
Korea.
In summary, this is a very interesting case that require further studies (
several weekends for you Chang) but my best shot is that this case is
really a description of a new stage or branching in the differentiation
process, something between myeloid and B cells. Our publication describing
similar cell lines to Chang s case is in press in Immunology letter and
will be out in a couple of months.
Chang: Again, please try to generate cell lines from these patient that
later you can do all the studies that you wish or dream.
Cheers
Rafael

>Correct me if I am wrong, but lymphoid and myeloid blasts express HLADR
>rather nicely. Also, CD45 negativity may be due to loss of expression
>completely, low level expression not detected, or failure to expresson
>surface. Neoplastic cells drop antigens at will.
>
>        Maryalice
>
>
>>Dear Chang
>>Your description is quite interesting and I would like to suggest a couple
>>(?) of markers that you may be considered worthy to study
>>1-Since your cells express quite high DR (96%), and since the cells  that
>>express highest DR are Dendritic cells-Langerhans cells, one marker that
>>could be interesting to check would be CD1a, and the markers associated to
>>Antigen presenting cells like CD11c, CD56, B7.1 and B7.2. (sorry, a lot of
>>work for the weekends of a third year resident). Please check the cells
>>also for Fc receptors (IgG and IgA receptors are express in some of those
>>cells)
>>2-The fact that your cells do not show CD45, does not mean that they are
>>negative for that marker, may be you have a cell that will express a splice
>>out isoform of CD45. My best shot is that your cell is CD45RO. I have
>>observed some cell lines that do not express CD45 but they are CD45RO. We
>>are going to present in Colorado at ISAC some cells with that
>>characteristics.
>>3-Please try to get cell lines from this patient. I recall the work from K.
>>Nielsson who, got a cell line form a patient and now after more that 25
>>years still is a very useful one, that cell line is U937 a monocytic cell
>>line. May be you have something quite similar. (it means, a lot of lab work
>>and  more weekends in the lab).
>>Cheers, good luck and keep in touch (What is your opinion Anna?)
>>Rafael
>>>Dear list members
>>>
>>>Have you ever seen a case of CD45 (leukocyte common antigen)-negative
>>>acute leukemia?
>>>
>>>The male patient was in his early 30's and visited our hospital with
>>>chief complaint of low platelet number. He felt fatigue and experienced
>>>easy bruisability but looked well.
>>>At the time of visit on Jan 6, 1998, the CBC data was WBC 6,000/uL,
>>>Hb 8.5 g/dL, platelet 24K/uL. The peripheral blood smear showed
>>>30% leukemic blasts and bone marrow revealed 89.6% medium sized leukemic
>>>blasts with high N/C ratio, fine chromatin, and absent to one nucleolus.
>>>
>>>Cytochemical stain was done; peroxidase (-), SBB (-), PAS (pinkish
>>>background
>>>staining), Non-specific esterase (-).
>>>
>>>Flow cytometric analysis of bone marrow aspirates revealed a predominant
>>>population of cells with a lymphoid light scatter. These leukemic blasts
>>>has following immunophenotype;
>>>
>>>  CD34 (+; 94%), HLA-DR (+; 96%), nuclear TdT (+; 92%)
>>>  CD33 (+; 53%), CD13 (+; 88%), CD61 (-)
>>>  CD7 (-), CD5 (-), CD2 (-)
>>>  CD20 (+; 27%), CD1
>>>9 (+; 90%), kappa (-), lambda (-), CD10 (+; 90%)
>>>
>>>and, interestingly CD45 was negative.
>>>
>>>We could find CD45-bright normal lymphocytes on CD45-RALS (right angle
>>>light scattle) dot plot thus false-negative for CD45 of these leukemic cells
>>>was ruled out.
>>>
>>>Anti-CD45 monoclonal antibody (Beckton-Dickinson Immunocytometry Systems,
>>>Cat No. 347463, USA) clone 2D1 conjugated with FITC (IgG1) was used at that
>>>time and we confirmed this CD45 negativity with immunostain on bone marrow
>>>aspirate smears using DAKO monoclonal antibody.
>>>
>>>Molecular and cytogenetic studies were also performed and demonstrated
>>>minor bcr/abl (e1a2) rearrangement and t(9;22), respectively.
>>>
>>>We concluded this case as a CD45-negative acute biphenotypic (myeloid and B
>>>lymphoid)leukemia.
>>>
>>>I tried to find out previously reported cases of CD45-negative acute
>>>leukemia
>>>but failed except some lymphomas.
>>>
>>>My questions are;
>>>
>>>1. Is this case the first one of CD45-negative acute leukemia?
>>>
>>>2. If it is not, could any one kindly tell
>>>me his/her experience or
>>>   the source of literature of reported cases?
>>>
>>>3. If it is the first one, I want to establish a new cell line with this
>>>case.
>>>   Could you give me a good reference or tips in doing this work?
>>>
>>>Any comment will be greatly appreciated.
>>>Thanks in advance.
>>>
>>>==================================
>>>Chang-Seok Ki, MD
>>>3rd-year Resident
>>>Dept. of Clinical Pathology
>>>Samsung Medical Center
>>>E-mail. kcdol@samsung.co.kr
>>>Tel. 82-2-3410-2707
>>>Fax. 82-2-3410-2719
>>>==================================
>>
>>
>>                                     \|/
>>                                    (o o)
>>________________________________oOo__(_)__oOo_________________________________
>>    ___/\_    | Rafael Nunez                  mailto:rafaeln@vetvir.unizh.ch
>>   /    o \/| | University Inst.for Virology  http://www.vetvir.unizh.ch/
>>  /        _| | Winterthurerstr. 266a         Telephone: (+41) 1 6358710
>> /_/\__/-\/   | 8057 Zurich SWITZERLAND       Faximile : (+41) 1 6358911
>>______________________________________________________________________________
>
>Maryalice Stetler-Stevenson
>Director Flow Cytometry Unit
>Laboratory of Pathology, NCI, NIH


                                     \|/
                                    (o o)
________________________________oOo__(_)__oOo_________________________________
    ___/\_    | Rafael Nunez                  mailto:rafaeln@vetvir.unizh.ch
   /    o \/| | University Inst.for Virology  http://www.vetvir.unizh.ch/
  /        _| | Winterthurerstr. 266a         Telephone: (+41) 1 6358710
 /_/\__/-\/   | 8057 Zurich SWITZERLAND       Faximile : (+41) 1 6358911
______________________________________________________________________________



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