Phil Chromo ALL

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Subject: Philadelphia Chromosome

Definition of Philadelphia chromosome (Ph)I hope is is ok to send

this =

from the search that I made. The last sentence contains some news

about =

meds.=20

I just remember how we searched for info when my mother was going

thru =

her Multiple Myeloma and hope this offers a glimmer of hope. We were

=

very thrilled to receive all the info we could.

Hannahs Nana

Philadelphia chromosome (Ph): The =

chromosome<http://www.medterms.com/script/main/art.asp?

articlekey=3D14018=

> abnormality that causes =

chronic<http://www.medterms.com/script/main/art.asp?

articlekey=3D2728> =

myeloid<http://www.medterms.com/script/main/art.asp?

articlekey=3D4483> =

leukemia<http://www.medterms.com/script/main/art.asp?

articlekey=3D4140> =

(CML). Abbreviated as the Ph chromosome.=20

The Ph chromosome is an abnormally short chromosome 22 that is one of

=

the two =

chromosomes<http://www.medterms.com/script/main/art.asp?

articlekey=3D2723=

> involved in a translocation (an exchange of material) with

chromosome =

9. This translocation takes place in a single bone marrow =

<http://www.medterms.com/script/main/art.asp?articlekey=3D4286>cell

and, =

through the =

process<http://www.medterms.com/script/main/art.asp?

articlekey=3D5054> =

of clonal expansion (the production of many cells from this one =

mutant<http://www.medterms.com/script/main/art.asp?articlekey=3D4470>

=

cell), it gives rise to the =

leukemia<http://www.medterms.com/script/main/art.asp?

articlekey=3D4140>. =

The discovery in Philadelphia in 1960 of the Ph chromosome was a =

landmark. It was the first consistent chromosome abnormality found in

=

any kind of malignancy. The discovery led to the identification in

CML =

cells of the BCR-ABL fusion =

gene<http://www.medterms.com/script/main/art.asp?articlekey=3D3560>

and =

its corresponding =

protein<http://www.medterms.com/script/main/art.asp?

articlekey=3D6554>. =

ABL and BCR are normal =

genes<http://www.medterms.com/script/main/art.asp?articlekey=3D15391>

on =

chromosomes 9 and 22, respectively. The ABL gene encodes a tyrosine =

kinase =

enzyme<http://www.medterms.com/script/main/art.asp?articlekey=3D3266>

=

whose activity is tightly regulated (controlled). In the formation of

=

the Ph translocation, two fusion genes are generated: BCR-ABL on the

Ph =

chromosome and ABL-BCR on the chromosome 9 participating in the =

translocation. The BCR-ABL gene encodes a protein with deregulated =

(uncontrolled) tyrosine kinase activity. The presence of this protein

in =

the CML cells is strong evidence of its pathogenetic (disease-

causing) =

role. The efficacy in CML of a drug that inhibits the BCR-ABL

tyrosine =

kinase has provided the final proof that the BCR-ABL oncoprotein is

the =

unique cause of CML.=20

The Ph chromosome is also found in a form of acute lymphoblastic =

leukemia<http://www.medterms.com/script/main/art.asp?

articlekey=3D13660> =

(ALL). It seems highly probable that this form of ALL is due to the

same =

chromosomal and molecular mechanisms as CML.=20

Philadelphia chromosome The hallmark of chronic myeloid leukemia

(CML). =

The Philadelphia (Ph) chromosome is an abbreviated chromosome 22 that

=

was shortchanged in an a reciprocal exchange of material with

chromosome =

9. This translocation occurs in a cell in the bone-marrow cell, and =

causes CML It is also found in a form of acute lymphoblastic leukemia

=

(ALL). On a molecular level the Philadelphia chromosome translocation

=

results in the production of a fusion protein. A large portion of a =

proto-oncogene, called ABL, on chromosome 9 is translocated to the

BCR =

gene on chromosome 22. The two gene segments are fused and ultimately

=

produce a chimeric protein that is larger than the normal ABL

protein. =

The malignant state is a consequence of this process. Understanding

this =

process led to the development of the drug imatinib mesylate

(Gleevec) =

the first in a new class of genetically targeted agents, a major

advance =

in cancer treatment..