| Disease |
CML: all CML have a t(9;22), at least at the molecular level (see below); but not all t(9;22) are found in CML, as already noted |
| Phenotype / cell stem origin |
Evidence exists for the involvement of the most primitive and quiescent hematopoietic stem cell compartiment (CD34+/CD38-, Thy1+): t(9;22) is found in myeloid progenitor and in B-lymphocytes progenitors, but, involvement of the T-cell lineage is extremely rare |
| Epidemiology | annual incidence: 10/106 (from 1/106 in childhood to 30/106 after 60 yrs); median age: 30-60 yrs; sex ratio: 1.2M/1F |
| Clinics | splenomegaly; chronic phase (lasts about 3 yrs) with maintained cell's normal activities, followed by accelerated phase(s) (blasts still < 15%), and blast crisis (BC-CML) with blast cells > 30%; blood data: WBC: 100 X 109/l and more during chronic phase, with basophilia; a few blasts; thrombocytosis may be present; low leucocyte alkaline phosphatases; typical acute leukaemia (AL) blood data at the time of myeloid or lymphoid -type blast crisis |
| Cytology | hyperplastic bone marrow; granulocytes proliferation, with maturation; followed by typical AL cytology (see t(9;22)(q34;q11)/AML, and t(9;22)(q34;q11)/ALL) |
| Treatment | aIFN therapy or allogeneic bone marrow transplantation (BMT), donor leukocytes infusions |
| Prognosis | median survival: 4 yrs with conventional therapy (hydroxyurea, busulfan), 6 yrs with aIFN therapy; allogeneic bone marrow transplantation may cure the patient; otherwise, the best treatment to date associates interferon a, hydroxyurea and cytarabine |
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835J22 + 1132H12 and 72M14 Cohybridization of (835J22 + 1132H12; ABL) and 72M14 (BCR) on a CML patient carrying the t(9;22) translocation. Note the splitting of (835J22 + 1132H12) (red signal) and the colocalization on Ph chromosome (Ph) -Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics |
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| Cytogenetics Morphological | the chromosomal anomaly persists during remission, in contrast with acute leukemia (AL) cases |
| Cytogenetics Molecular | is a useful tool for diagnostic ascertainment in the case of a 'masked Philadelphia' chromosome, where chromosomes 9 and 22 all appear to be normal, but where cryptic insertion of 3' ABL within a chromosome 22 can be demonstrated |
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Cryptic insertion of BCR within chromosome 9. FISH using the Vysis LSI BCR/ABL Dual Color, Dual Fusion Translocation Probe - Courtesy Karolien Beel, Geneviève Ameye and Lucienne Michaux, CME, UZ Leuven |
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| Additional anomalies | 1. may be present at diagnosis (in 10%, possibly with unfavourable significance), or may appear during course of the disease, they do not indicate the imminence of a blast crisis, although these additional anomalies also emerge frequently at the time of acute transformation;
2. these are: +der(22), +8, i(17q), +19, most often, but also: +21, -Y, -7, -17, +17; acute transformation can also be accompanied with t(3;21) (q26;q22) (1% of cases); near haploidy can occur; of note, although rare, is the occurrence of chromosome anomalies which are typical of a given BC phenotype (e.g. t(15;17) in a promyelocytic transformation, dic(9;12) in a CD10+ lymphoblastic BC ...); +8, +19, +21, and i(17q) occur more often in myeloid -rather than lymphoid- blast crises |
| Variants | t(9;22;V) and apparent t(V;22) or t(9;V), where V is a variable chromosome, are found in 5-10% of cases; however, 9q34-3'ABL always joins 22q11-5'BCR in true CML; the third chromosome and breakpoint is, at times, not random. In a way, masked Philadelphia chromosomes (see above) are also variants. |
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