Leukemia and WBC count

[Seph]

Can someone explain to me, why the WBC count is elevated in leukemia?

Goljan and a couple other texts talk about how the WBC count is elevated, but mention that lymphoblasts or other neoplastic cells may only be >20/10% of the total count. For example:


About acute leukemias:
a. Ranges from <10,000 cells/mm (normal) to >100,000 cells/mm
b. Blast cells are usually present.

About chronic leukemias:
a. Count is similar to that of acute leukemia
b. Blast cells are usually <10% of the total WBC count.

So, my question is, where do the rest of the increased WBCs come from if the majority of cells may or may not be neoplastic?

Thanks.

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[Ionian]

I'll try to explain the dogma as I see it.

Acute Leukemias/lymphomas = Mutations of differentiation (can't mature), and proliferation (can be overproduced/overgrow).
Blasts proliferate and build up (because they aren't becoming mature) "crowd out" the marrow --> > 20% blasts ---> extramedually hematopoesis.

Chronic "Myeloproliferative disoders" = Early (blast) mutations of activation/proliferation, but retain the ability to differentiate, thus no crowd out.
They can differentiate, some times to non-neoplastic cells (why many names are not called "Leukemia" and are "chronic myeloproliferative" such as P. vera, RBC (anucleate) aren't neoplastic cells, but their precursor were. Many times WBCs of all categories are overproduced because the early (sometimes common) precursors have activating mutations.

CLL on the other hand = Usually late mutations of increased survival. Like B cell lymphoma, expressing increased BCL-2, make it resistant to apoptosis.

ALL/AML = Cell lines can't mature
CML = Mature cells are overproduced
CLL = Mature cells wont die

Idk if that helps...

 

[Seph]

Thanks for the help.

I get why the myeloproliferative disorders give rise to elevated blood counts. What i don't get is how can a WBC be elevated in an acute leukemia when only a fraction of those cells can be neoplastic blasts.

 

[Missorleans]

It's not a fraction of a normal WBC, it's a fraction of an elevated WBC. You're making too many WBCs.

 

[Seph]

Are you making lots of normal WBC or lots of neoplastic blasts? In acute leukemia blasts dont mature, so how can you be making more WBC? You should be making less because of crowding.

 

[Ionian]

Are you making lots of normal WBC or lots of neoplastic blasts? In acute leukemia blasts dont mature, so how can you be making more WBC? You should be making less because of crowding.

Some lines start with a proliferating mutation, then further 'more mature' lines but still precursors aquire defects which prevent differentiation.
There are thus over proliferations, and blocks. Immature cells can escape into the blood, and I believe extramedullaryhematopoeisis also contributes.

 

[Seph]

Thanks ionian, it makes sense.