GENES VERSUS CHROMOSOME ABNORMALITY

AS WE MOVE FORWARD, ABNORMALITY IN GENES WILL BE MORE IMPORTANT AS FAR AS CLINICAL RELEVANCE IS CONCERNED.  ONCE UPON A TIME CHROMOSOME ABNORMALITY WAS RELEVANT BUT WITH THE NOW RISING INTEREST IN TARGET THERAPY, THE GENE IS THE FOCUS OF ATTENTION.
IT IS TRUE KNOWING THAT ABNORMALITY OF THIS AND THAT CHROMOSOME WAS RARELY RELEVANT FROM THERAPEUTIC STAND POINT UNTIL YOU DISSECT THE GENES INVOLVED.  DEL OF 5q IN MYELODYSPLASIA WAS THE MOST CITED EXAMPLE OF HOW REVLIMID HELPED THE CHROMOSOMAL DETECTION EXAMPLE, BUT THE FACT IS, IT IS STILL UNCLEAR WHAT GENES IN THIS SCENARIO ARE AT PLAY.  AND  THE NEED TO DO BETTER AT TARGETING CALL FOR GENE IDENTIFICATION RATHER THAN GLOBAL CYTOGENETIC STUDIES!

LOOKING AT THIS CLOSER, EUROPEAN INVESTIGATORS ARE NOW THE TRUE MECHANISM OF ACTION OF SOME WELL ESTABLISH MEDICATIONS.  AZACITIDINE FOR EXAMPLE IS NOW INCREASING RECOGNIZED AS A IMMUNE-MODULATOR BECAUSE OF ITS EFFECT ON T-CELL.  IT IS ACTUALLY TRUE THAT IF YOU FOLLOW THE NF-kB, C-JUN AND FOS (INVOLVEMENT OF GROWTH FACTORS), YOU QUICKY WILL ARRIVE IN THE EPIGENIC REGION WHERE HYPOMETHYLATION, SPLICING, m-ARN TRANSFERASE AND OTHER RELEVANT ACTIVITY CO-MINGLE AND CO-ACTIVATE AT RAPID PACE MAKING DISSECTION AND ATTRIBUTION OF ROLE DICEY OR TRICKY.

ON OTHER FRONT, STILL LOOKING INTO MECHANISM OF ACTION OF KNOWN DRUG, THE THALIDOMID STORY GOT A NEW DEVELOPMENT WITH THE ANNOUNCEMENT THAT FDF8 WAS THE TERATOGENIC BASIS OF THALIDOMID ACTIVITY!  IF BY TERATOGENESIS, WE MEAN MORPHOLOGIC ABNORMALITY, THIS WILL BE A SIGNIFICANT DEVELOPMENT.  HOW IS FDF8 RELATED TO ANGIOGENESIS?  IS FDF8 RELEVENT ONLY TO THALIDOMID OR SHOULD ALTERATION HERE BE BROADLY APPLIED TO CHECK ALL DRUGS FOR TERATOGENIC POTENTIAL? HOW IS FDF8 RELATED TO MESENGIAL TRANSFORMATION...MUCH IS TO BE LEARNED YET!  SUFFICE IS TO SAY THAT A GENE INVOLVING SIGNIFICANT MORPHOLOGIC CHANGES IS DEFINITELY AN IMPORTANT GENE!