SUPPRESSION OF NF-kB IS ONE OF THE DOMINANT EVENT IN ACUTE MYELOID LEUKEMIA,

As we explore the major genes involved in Acute Myeloid leukemia, we quickly realize that the main initiating event is located in the Core binding factors or complex proteins located at the Histone-DNA.  At this level we already uncovered that the nature of molecule interacting and  involved are considerably important, and fundamentally different when you speak about Hematological neoplasm versus solid tumor.
Globally, they appear to be several levels of action:

1.  Nature of components of Histone (H1A, H2A etc..) as cover of DNA. 
2.  Complex involved in Histone remodeling  (H1Ax)
3.  Portion Alpha-subunit of protein complexes attached to the DNA to control its expression, and here we find the RUNX which control Hematologic differentiation
4. Portion of Alpha subunit that actually ensure just clear attachment to DNA so that the Histones do not run in the nuclear  solution.  But be careful in fact most of the time if not always, the place of attachment of histone is not random and varies according to nature of tissue involved.  That is Histones attachment contribute to gene silencing and tissue differentiation.
5. Then there Beta subunits which send tentacles dealing with
    5.1-pure Histone Deacyl transferase activity
    5-2- DNA uncoiling and coiling
    5.3- Interaction with Regulators
    5.4-Interactions with cytoplasmic  signal trasductions (MAPK, FOS/c-JUNK, RAS,PI1K ,VEGF)
    5.5-output back to the cytoplasm to inhibit or activate regulators of signal transduction.  The control of signal transduction pathways is done through enzymes production but through activation of switches (E3, SOS) and through control of Ubiquitination and the MDM2
   5.6- DNA replication controlled through P53, and check-point control molecules.
    5.7-signal to Mitochondria, the Ribosome AND AT C-MYC
  etc. (Transcription factors)
The Centrosome have a DNA attachment portion and an endonucleases portion and some endonucleases find their way to  this area of histone-DNA.

Suffice is to say that in AML, the RUNX is involved to ensure Hematologic differentiation, Many regulators are involved, but suppression of the NF-kB and therefore suppression of the TGF is an significant find!
One now speculate as to why it is so.  AND WITHOUT HESITATION, ONE CONCLUDE THAT IT IS BECAUSE AML DOES NOT NEED TO FORM A MASS!  THE SUPPRESSION OF TGF CAN BE INSUFFICIENT HOWEVER, AND A GRANULOCYTIC SARCOMA IS CREATED BUT THIS IS RARE.

(CLEARLY SOME OF THE CONCEPTS PRESENTED HAVE STILL TO BE FULLY VISITED BY RESEARCHER AND READERS-READ MORE TO ESTABLISH THIS IS SO!)

IT IS INTERESTING TO NOTE THAT WHILE IN THE STRUGGLE IS AT THE RUNX IN AML, IN BLADDER CANCER THE TGF IS IS FULL SWING, DNA REPAIR IS IN FULL SWING, BUT ALSO EVENTS AT THE HISTONE MODULATION AS ALSO IN FULL SWING

Bladder cancer in 2012:
Prevalence 73.5 Thousand patients in the USA
Deaths 14.9 thousands died with this disease.
Only 15% of patients have localized disease
50% of patients who have muscle invasion will eventually progress, Median survival in Metastatic disease is 14 months.
Smoking is an established risk factor for Bladder cancer

When the Bladder Muscle is invaded, Giving 3 cycles of chemotherapy (MVAC) before surgery is standard of care and lead to a 77 months median survival Versus 46 months with surgery alone (SWOG 8710.) . But only 20% of people receive Neoadjuvant Chemotherapy.   Mostly because the disease affect the elderly who's perfomance is judged poor for the chemotherapy, because of renal failure which preclude use of Cisplatin, and related comorbidilties which would make chemotherapy hazardous.

Genes reported in Bladder cancer:

MRE11
RAD50
NBS1
ATM
_______________________________________________-----These 4 genes all involves a close pathway.   Under chemical effect there is breakage of double chains DNA in bladder cells  The DNA Break trigger stimulate ATM by phosphorylation or similar activation, MRE1-RAD50-NBS1 is a complex molecule which must allow repair of the breakage by exposing it through "histone remodeling".  Mutations here will hamper this sequence of Activity.  "Breakage of DNA" and HOP, P53 activation is not far.  This is why intact P53 or wild type marks an early cancer. and Mutation of P53 is more a sign of an advanced Bladder cancer.
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H2AX-during Histone remodeling H2Ax replace H2A and participate in the triggering of check point arrest and therefore a key point to the Histone complex activity which is to control DNA transcription.
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CSS (Calpain family) contain DeK1 and CysPc and other anchors/molecules (Now you are going closer to treating AML)
Resistance to Cisplatin: ERCC1
Bcl-2
Overexpression of HRAS (in early disease)
70% have Mutation in FGFR3
P53 and Rb more advanced disease
P21, and P16 are also bad prognosis predictors.

NMP22 may be identified in the Urine for early detection of superficial bladder cancer

Clement Albert (Dr Mutombo Kankonde ) on Ubetoo.com!

Gender	Male
City	El Paso, Texas
Country	United States

This member last logged in 10:44 PM yesterday and has logged in 1 895 times, his profile has been viewed 8 910 times.For those who don't know me yet: My name is Clement Albert.I am a singing doctor and an artist specializing in making songs about situations that I find difficult to talk about. I live at the confluent of several cultures and sing my commitment to life and love.