vit. D levels vs. tumor burden or lysis

[Guest guest]

Re: Vitamin D insufficiency and prognosis in chronic

lymphocytic leukemia (CLL)

At 01:09 PM 11/4/2010, Gach wrote:

>As my CLL progressed and my WBC gradually increased from 15,000 to

>285,000, another test showed very low vitamin D levels, even though

>I had maintained the 2,000 IU daily supplementation all along. My

>conclusion is that it was CLL progression that interfered with the

>absorption of vitamin D..

Similarly, my blood levels of vitamin D have moderately decreased as

my WBC counts have moderately increased.

I have thought that a possible explanation for decreasing blood

levels of vitamin D with increasing WBC counts might be because CLL

cells have been observed (2003, C.Pepper et al.) to have high

expression of vitamin D receptors, which might reach a level high

enough, as WBC counts rise, such that blood levels of vitamin D might

be significantly decreased because of binding to these

receptors. One could do some calculations to assess whether that

might be at least a theoretical possibility.

However, the authors (Shanafelt et al.) of the current Blood paper,

observed no relationship between serum blood levels of vitamin D and

indicators of tumor burden (e.g. Rai stage). See the " SNIP " s from

their " Discussion " below.

These observations of Shanafelt et al. do not absolutely exclude the

possibility of CLL being involved (in some patients) in lower blood

levels of vitamin D, but it may not be a simple relationship with CLL

cell burden.

For example, several years ago, it was theorized that when 'sickled'

red blood cells (in patients with sickle cell anemia) are broken down

( " lyse " ) and their hemoglobin is leaked into the blood (hemolysis),

that 'free' hemoglobin can bind and remove an important vasodilator

(nitric oxide), locally depleting nitric oxide in blood vessels,

causing local vasoconstriction and resultant pain.

Likewise, maybe it isn't the level of vitamin D receptors on intact

CLL cells that is important. Maybe what is important is the amount

of free vitamin D receptors leaked into blood when CLL cells are

broken down (e.g. via apoptosis). As such, it would be interesting

to measure in CLL patients the rate of CLL cell apoptosis (and/or

'free' vitamin D receptors) vs. serum vitamin D levels. Again, one

could do some calculations to assess whether that might be at least a

theoretical possibility.

Al Janski

Blood First Edition Paper, prepublished online November 3, 2010; DOI

10.1182/blood-2010-07-2956; Tait D. Shanafelt et al.

http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2010-07-295\

683v1

Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia (CLL)

DISCUSSION:

SNIP......

The vitamin D receptor is highly expressed by CLL B-cells relative to

normal B and T-cells and pharmacologic doses of vitamin D derivatives

developed as therapeutic compounds have been shown to induce caspase

3 and 9 dependent apoptosis (e.g. mitochondrial pathway) of CLL

B-cells in vitro.

[Ref. #33: C. Pepper et al., Blood, 1 April 2003, Vol. 101, No. 7,

pp. 2454-2459]

SNIP..........

One question that arises is whether serum vitamin D levels could be

influenced by tumor burden (e.g. higher ALC or greater nodal disease

could lead to vitamin D binding and lower serum levels). [Ref.

37-40] In this regard, serum vitamin D levels had no relationship

with Rai stage in either the discovery cohort or the confirmation

cohort and also had no correlation with ALC in the 229 patients in

the discovery cohort who had an ALC measured within 2 months of the

vitamin D measurement. Furthermore, serum vitamin D levels remained a

predictor for TTT among both Rai 0 patients and patients with stage

Rai >1 when these groups were evaluated separately and on the MV

analysis controlling for disease stage. Thus, while an important

aspect for future investigations, it does not appear that the

observed relationship between serum vitamin D levels and clinical

outcome is related to an interaction between vitamin D levels and tumor burden.