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Comment 15

Please cite this contribution as follows: Kshama Gupta. Dear Dr. Alexey, Many thanks for your comment and making. Blog comment, Maximow Award contest, June 2012. Cell Ther Transplant/Maximow Award, June 2012;blog-comment_15. doi:10.3205/maximowaward_2012_blog-comment_15

This contribution is provided under the following license: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Kshama Gupta. June 4, 2012 at 7:07 pm 

Dear Dr. Alexey,

Many thanks for your comment and making this a very interactive platform. I highly appreciate for your read and for all the valuable information you conveyed. Though not being a clinician, I would agree as you state / with given references that “myeloid biased-HSC” could also lead to multi-lineage engraftment and which infers that there’s no black and white. However, in line with the same, I had tried to highlight that there is yet much needed research going on to decipher the various differentiation routes [the quoted models], that these sub-populations would / may undertake, to bring about such plethora of functions. This further confers that the information we have today, is limited by our ability to really distinguish between these cells cause of the multi-lineage effects they exhibit (under the influence of Microenvironment / stimuli), and hence are heterogenous. Thus, it would be of significance to understand and classify them at the single cell level.

In agreement with as you said, this may not be very applicable for the patients who must require the whole marrow transplantations but it’s a very relevant aspect for advanced targeted therapies to various kinds of hematological dis-orders. Many leukocytopenia occur by the differentiation block at some or the other progenitor stages as known well also in case of congenital neutropenias (Welte K., Skokowa J. et al.). Therapies currently under effect are quite successful but there still are deleterious clinical observations or out comes as secondary leukemia found in some patients after long term treatments. The exact cause of these may not be the therapy per say but down stream / inherent defects at the molecular level. Some of these are harbored by the specific subset of progenitors. To target the hematopoietic stem–progenitor pool or to perform whole marrow transplantation may not always be a feasible approach and in cases would abrogate the other lineages as well.

Delineating the individual steps in differentiation cascade v.i.z. when / which progenitor population undergoes proliferative burst, what path it takes, in response to what stimuli and to what counts in normal as compared to diseased has quite lead to our better understanding of the patho-mechanisms involved. Along with, to exploit the behavior and characteristics ( Molecular / functional) of these sub-populations have contributed to several challenging advancements in the regulation/ treatment of various hematological disorders.

As we all have agreed at some point or the other during our discussion that HSC population is heterogenous, and as quoted by you previously, even in clinics, its this mixed-hematopoietic progenitor cell based therapy which infact furnishes the properties of STEM cells, otherwise; hence we yet need more information to really say which cells exactly are the actual “initial point“ (as said by Ilya) and how do their descendents take their path. Rather than limiting our selves with calling this potential heterogenous population as HSC, with the current knowledge of this pool, a further step in the precise identification and categorization of the progenitor / sub-populations would not only open gates for new and better therapeutic approaches but would help us understand how our complex physiology had evolved.

Thanking you again for sharing your ideas and for all the valuable inputs / discussion …

This contribution is provided under the following license: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Please cite this contribution as follows: Kshama Gupta. Dear Dr. Alexey, Many thanks for your comment and making. Blog comment, Maximow Award contest, June 2012. Cell Ther Transplant/Maximow Award, June 2012;blog-comment_15. doi:10.3205/maximowaward_2012_blog-comment_15

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