The Philadelphia chromosome is identified

Historical milestone — this page describes an event dated 1960. It is not current breaking news.

A chromosome that was the wrong size

NCI's own timeline of cancer research puts it in one sentence. In 1960, Peter Nowell and David Hungerford described an unusually small chromosome in the cancer cells of patients with chronic myelogenous leukemia.

It became known as the Philadelphia chromosome. NCI notes it turns up in the leukemia cells of 95 percent of people with CML.

At the time this was a curiosity. Nobody could treat it. What it did was change a belief: that cancer was a disorder of cells in some vague sense, rather than something with a specific, findable, physical cause you could point at down a microscope.

What the small chromosome actually is

NCI now describes the mechanism plainly. In CML, part of the DNA from one chromosome moves to another. Pieces of chromosomes 9 and 22 break off and trade places.

The ABL1 gene from chromosome 9 lands next to the BCR gene on chromosome 22. The two fuse into one gene, BCR::ABL1. The shortened chromosome 22 that carries it is the Philadelphia chromosome.

That fused gene makes a protein called a tyrosine kinase, an enzyme that tells cells to divide. This one is stuck in the on position. The result, NCI says, is that too many stem cells become white blood cells.

One thing worth stating clearly: NCI notes the Philadelphia chromosome is not passed from parent to child. It happens in a blood cell during a person's life.

Our page on CML pathology and molecular results explains how this shows up on a report.

When to get checked

CML often causes nothing at all. NCI says so directly: sometimes it produces no symptoms, and it is found on a blood count done for another reason.

When it does show itself, NCI lists:

• Fatigue.
• Weight loss for no known reason.
• Drenching night sweats.
• Fever.
• Pain or a feeling of fullness below the ribs on the left side.

That last one is the specific one. The spleen sits under the left ribs, and in CML it enlarges as it fills with white cells. A doctor can often feel it. Fullness or discomfort there, especially with fatigue and night sweats, is worth an appointment.

There is no screening test for leukemia in the general population. Diagnosis starts with a complete blood count with differential, then bone marrow tests and genetic testing for the Philadelphia chromosome and the BCR::ABL1 fusion.

What it took to make it useful

The path from 1960 to a treatment ran 41 years.

FDA records show Gleevec, the brand name for imatinib mesylate, was approved on May 10, 2001 under priority review. NCI's timeline describes what the trial showed: imatinib targets the protein made by the Philadelphia chromosome, and treatment turned a usually fatal disease into a manageable one.

Imatinib was the first of a class. NCI now lists five tyrosine kinase inhibitors used in CML: asciminib, imatinib mesylate, dasatinib, nilotinib and bosutinib. They are taken as tablets. Our page on imatinib covers what taking one involves, and our page on targeted therapy covers the wider idea.

One practical detail from NCI's summary is easy to miss: bariatric surgery can block absorption of oral tyrosine kinase inhibitors, which limits how well they work.

The numbers, then and now

SEER tracks five-year relative survival for CML back to 1975. In that year it was 17.99 percent.

For cases diagnosed from 2016 to 2022, it is 71.1 percent. The most recent single-year figure in the SEER series, for 2018, is 72.39 percent.

An estimated 9,650 new cases and 1,170 deaths are projected for 2026. The median age at diagnosis is 67, and the median age at death is 77.5.

Those figures describe a group across the whole country. They do not describe any one person. But the shape of that line, from under a fifth to around seven in ten, is what a molecular target eventually bought.

What to keep in perspective

• The 1960 finding was a visible oddity in a chromosome. What it meant took years more work to establish, and the gene fusion behind it came later still.
• The discovery changed nothing for patients in 1960. Forty-one years passed before a drug aimed at it was approved.
• CML is unusual. It has one dominant driver that a tablet can block. Most cancers do not, which is why this success has been hard to copy.
• Survival figures cover a whole population over years and are shaped by age, phase at diagnosis and other health conditions.
• This is a summary of a historical finding, not advice about your own care.

Sources

• NCI, Milestones in Cancer Research and Discovery — https://www.cancer.gov/research/progress/250-years-milestones
• NCI PDQ, Chronic Myeloid Leukemia Treatment (Patient Version) — https://www.cancer.gov/types/leukemia/patient/cml-treatment-pdq
• FDA Drugs@FDA, imatinib mesylate (Gleevec, NDA 021335) — https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=021335
• SEER Cancer Stat Facts, Chronic Myeloid Leukemia — https://seer.cancer.gov/statfacts/html/cmyl.html
• NHGRI, Talking Glossary of Genomic and Genetic Terms: Translocation — https://www.genome.gov/genetics-glossary/Translocation

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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