A) ABL: located on the long arm of chromosome 9. Its breakpoints are variable and can occur upstream of the first alternative exon 1b, downstream of the second alternative exon 1a, and between both (left arrows). BCR: located on the long arm of chromosome 22, which has three breakpoints: m-bcr, M-bcr and µ-bcr; B) the fused messenger RNA molecules e1a2, e13a2, e14a2 and e19a2 exons junctions (ABL exons in light grey and BCR exons in dark grey) and their respective generated chimeric proteins (p190, p210 and p230); C) reciprocal translocation between chromosomes 9 and 22 with the derived chromosomes.
BCR: breakpoint cluster region; ABL: Abelson proto-oncogene; m-bcr: minor breakpoint cluster region; M-bcr: major breakpoint cluster region; µ-bcr: micro breakpoint cluster region; RNA: ribonucleic acid.
A) ABL: located on the long arm of chromosome 9. Its breakpoints are variable and can occur upstream of the first alternative exon 1b, downstream of the second alternative exon 1a, and between both (left arrows). BCR: located on the long arm of chromosome 22, which has three breakpoints: m-bcr, M-bcr and µ-bcr; B) the fused messenger RNA molecules e1a2, e13a2, e14a2 and e19a2 exons junctions (ABL exons in light grey and BCR exons in dark grey) and their respective generated chimeric proteins (p190, p210 and p230); C) reciprocal translocation between chromosomes 9 and 22 with the derived chromosomes.
BCR: breakpoint cluster region; ABL: Abelson proto-oncogene; m-bcr: minor breakpoint cluster region; M-bcr: major breakpoint cluster region; µ-bcr: micro breakpoint cluster region; RNA: ribonucleic acid.
| Chronic phase | Accelerated phase | Blast phase/blast crisis | |
|---|---|---|---|
| Clinical features | Asymptomatic or mild symptoms. Fatigue, weight loss and anorexia. Hypermetabolism. Splenomegaly, hepatomegaly and mild lymphadenopathy. Abdominal discomfort and acute pain in the left upper quadrant |
Symptomatic patients (not all). Fever, bone pain, bleeding and sweating. Splenomegaly. Organ infiltration |
Aggressive presentation. Symptoms similar to those of the accelerated phase worsened. Fever, sweats, bone pain, weakness, loss of sense of well-being and splenomegaly. The patient no longer responds to the medication previously used, contributing to a higher risk of malignancy presentation |
| Hematologic features | Moderate anemia. Hypercellular bone marrow. Large proportion of basophils, eosinophils, neutrophils, metamyelocytes and myelocytes. Increased number of megakaryocytes. Granule-erythroid ratio above 10:1. Leukocytosis, often above 100,000 cells/mm3. Increased reticulin deposition within bone marrow |
Worsening of anemia. Blood or bone marrow blasts percentage of 10%-19%. Basophils in blood ≥ 20%. Persistent thrombocytopenia (˂100 × 109/l) unrelated to therapy. Increased white blood cell count unresponsive to therapy |
Blood or bone marrow blasts ≥ 20%. Similar to acute leukemia or presence of organs or tissues infiltration by blasts. Severe anemia, increase in the number of nucleated red blood cells. Bone marrow fibrosis. Decrease in the total number of leukocytes and myelocytes |
| Cytogenetic features | Additional abnormalities in positive Ph (excluded Y loss, Ph variants and constitutional abnormalities) | Additional clonal chromosomal abnormalities in positive Ph at diagnosis, including "major route" abnormalities (second Ph, +8, isochromosome 17q, +19), complex karyotype, abnormalities of 3q26.2. Any new clonal chromosomal abnormality in positive Ph that occurs during therapy |
Additional abnormalities in positive Ph and Ph abnormalities variants |
