Philadelphia Chromosome

Lenap · Sep 9, 2004

the philadelphia chromosome results from a mutation called a translocation (two chromosomes break, then parts from each chromosome switch places). in cml, the translocation occurs between chromosomes 9 and 22 (human dna is packaged in 23 pairs of chromosomes) and produces a new, abnormal gene called bcr-abl. this abnormal gene produces bcr-abl tyrosine kinase, an abnormal protein that causes the excess wbcs typical of cml.

the philadelphia chromosome is an acquired mutation-that is, a person is not born with it and it is not passed on to their children. exactly why the philadelphia chromosome forms is unknown in most cases, although exposure to ionizing radiations (such as during the atomic bomb explosions in japan) has been shown to cause cml.

cml is divided into three phases depending on the maturity of the leukemia wbcs.

chronic phase there are mostly mature leukemia wbcs in the blood and bone marrow and there may be no symptoms of leukemia. this phase lasts from several months to several years, with an average duration of five years.

accelerated phase there are some immature leukemia wbcs in the blood and bone marrow (between 5 percent and 30 percent). patients may have fever, poor appetite and weight loss. the leukemia cells may have new chromosome changes, in addition to the philadelphia chromosome.

acute phase also called blast phase or blast crisis. in this phase, there are mostly immature wbcs in the blood and bone marrow (more than 30 percent). symptoms such as anemia and recurring infections are typical.

i hope this helps. here are some links that have more information:

http://www.antigenics.com/diseases/cml.html

http://gslc.genetics.utah.edu/units/disorders/karyotype/reciprocal.cfm

http://en.wikipedia.org/wiki/philadelphia_chromosome

http://users.rcn.com/jkimball.ma.ultranet/biologypages/c/cml.html

Lenap · Sep 9, 2004

sorry, did not read your question correctly. tried to look up what it means to have an absent philadelphia chromosome. this is what i found:

"about 40 years ago two forms of chronic myelocytic leukemia (cml) were recognized in children. one had the typical features of cml of adulthood and usually appeared in children older than 4 years; the other affected younger children and presented as a myelomonocytic proliferation associated with hemorrhage, infection, lymphadenopathy, and skin rash. the prognosis of the latter group of patients was invariably poor.1-3 in subsequent attempts to identify clinico-biological features that would further discriminate between these leukemias, reisman and trujillo4 found the absence of the philadelphia (ph) chromosome to be a hallmark of the juvenile-type entity (jcml). signs of disturbed erythropoiesis were also reported to be typical of jcml, including low levels of hemoglobin (hb) a2 and erythrocyte carbonic anhydrase,5 together with a marked increase of hbf,6 and glucose-6-phosphate dehydrogenase activity.7 maurer and others concluded that jcml is accompanied by a reversion to fetal-like erythropoiesis.8-10 the observation of chromosomal translocations in leukemic bone marrow cells of different lineages suggested that the pathologic process might involve a multipotent stem cell."

here is a link to a full article:

http://www.bloodjournal.org/cgi/content/full/90/2/479

luvrn · Sep 9, 2004

Thank you very much....I read some articles on the net but just didn't understand them fully....I thought NOT having the Philadelphia chromosome was a good thing, but after reading some articles and your reply I guess it isn't. The young man didn't even know what it meant. I blame the Drs. for not explaining things better. Again thank you for the articles and I will pass them along to the family.

Lenap · Sep 10, 2004

This is a really sad case. It always breaks my heart to hear anyone has a bad prognoses. I once had this man with lung ca w/ mets to his brain. Only got diagnosed after family brought him to hospital with c/o weakness and personality change. Md told family his prognosis would be few months left to live. On the 3rd day after diagnosis just as we were preparing him for his 1st tx of chemo and rad, pt died right in front of me and his family. It was really sad and I found myself crying along with the family. My point really was that sometimes even docs don't really know how bad the prognosis is. I am glad you'll be able to inform patient and his family, even though its doc's job to have this talk with them about dx, prognosis and tx.

Anyway, I am glad to be any help.

leslie :-D · Sep 10, 2004

i am recalling a gentlemen i received on a friday noc, in my hospice unit.

his entire pelvic cavity was filled with tumors, yet he arrived with a gtube.

his family, extremly anxious, arrived with him, telling me that the onc doctor said he had around 2-3 months to live.

i could not administer any meds through his gtube (never mind his fdgs) because he was so obstructed.

with my experience, i very gently told them that i could not see him surviving the 2-3 months, but more like 2-3 DAYS.

the family, very upset, called the onc, who called me, chewing me out.

i gently but firmly told the onc that this patient's time was extremely ltd.

the family stayed throughout fri noc and were still there on sun am when i returned for a double shift.

on sun noc the family was SO stressed and anxious that i told them they needed to go home so the patient could rest.

they finally conceded, went home.

within 15 min after they left, my patient was still anxious. i gave him more ms04; he told me thank you for everything, and peacefully took his last breaths.

he very much was ready to go but did not want his family there.

my point? oncologists don't always see the imminency of the patient's condition but rather give prognosis according to other data, unrelated to what the patient is presenting with.

and i strongly feel that there are many ca patients who would benefit from hospice services much sooner than they typically receive.

leslie

chemoqueen, BSN, RN · Oct 7, 2004

Thank you Lealie for being advocate for your patient. Families deserve to know what' going on in order to make whatever ammends they need too (as you know, there are alot of guilty feelings when a loved one becomes terminal) and to have closure. As I told you yeaterday--Hospice nurses are MY heros!

Phyllis

i am recalling a gentlemen i received on a friday noc, in my hospice unit.
his entire pelvic cavity was filled with tumors, yet he arrived with a gtube.
his family, extremly anxious, arrived with him, telling me that the onc doctor said he had around 2-3 months to live.
i could not administer any meds through his gtube (never mind his fdgs) because he was so obstructed.
with my experience, i very gently told them that i could not see him surviving the 2-3 months, but more like 2-3 DAYS.
the family, very upset, called the onc, who called me, chewing me out.
i gently but firmly told the onc that this patient's time was extremely ltd.
the family stayed throughout fri noc and were still there on sun am when i returned for a double shift.
on sun noc the family was SO stressed and anxious that i told them they needed to go home so the patient could rest.
they finally conceded, went home.
within 15 min after they left, my patient was still anxious. i gave him more ms04; he told me thank you for everything, and peacefully took his last breaths.
he very much was ready to go but did not want his family there.
my point? oncologists don't always see the imminency of the patient's condition but rather give prognosis according to other data, unrelated to what the patient is presenting with.
and i strongly feel that there are many ca patients who would benefit from hospice services much sooner than they typically receive.
leslie