| Disease |
Acute lymphoblastic leukemia |
| Phenotype / cell stem origin |
Leukemic cells were positive for CD34, CD10, CD19, CD20, CD38.
| Patient | Leukemia | Age/Sex | WBC 109/L | Karyotype | Outcome | References | | 1 | B-precursor ALL | 4/M | 20 | 46,Y,der(X)t(X;8)(q28;q11.2),t(9;22)(q34;q11),t(8;14)(q11.2;q32),add(17)(p13) | CR; Relapsed after 23,5 mths | Kaleem et al., 2000 | | 2 | Common B ALL | 19/M | 17 | 46,Y,der(X)t(X;8)(q28;q11.2) | CR; Complex medullar and CNS extramedullary relapses after 10 mths and 13 mths; CR after BMT; Isolated post-transplant CNS relapse; died after 29 mths after diagnosis | Present case, 2016 |
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| Epidemiology | Extremely rare karyotypic event in ALL; both ALL patients were males (aged 4 and 19 years). |
| Clinics | Among the characteristic laboratory features were a low WBC at presentation. One of the two ALL patients had a few reddish skin nodules 5-7 mm in diameter, moderate hepatosplenomegaly. No patient had a mediastinal mass or central nervous system involvement at diagnosis, but one patient had CNS extramedullary relapses, including post-transplant. |
| Cytology | Bone marrow are hypercellular with 54.4% lymphoblasts of L1 or L2 morphology. They were negative for myeloperoxidase, whereas most of them positive for PAS stain. Erythropoiesis and myelopoiesis were decreased. Erythropoiesis had signs of megaloblastosis. Megakaryocytopoiesis: hypolobular and polyploid megakaryocytes. |
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| Micro- and macrogenerations of lymphoblasts. Blasts had rounded nucleus and finely dispersed chromatin with well-contoured nucleoli. Iconography courtesy Valentina Kravtsova. |
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| Pathology | Histopathology of the skin nodules was remarkable for interstitially located groups of small- and middle-sized lymphoid blast-like cells, which were positive for TdT, PAX-5, CD20, CD10, negative for T-cell and myeloid markers and had a very high proliferation rate (Ki-67 index above 90 %). myc oncogene product was additionally assessed with immunohistochemistry (clone Y69). Over 90% of blast cells in the skin appeared to be positive for myc, although staining pattern was markedly heterogeneous. The brain tissue (at post-transplant relapse) contained a dense cellular infiltrate composed of middle-sized PAS-positive blasts with oval or round nuclei, containing 2-3 small nucleoli. Tumor cells were uniformly positive for TdT, CD19, PAX-5, and CD79a and had a very high Ki-67 proliferation index. myc oncogene product was demonstrated in over 85% of cells with heterogeneous staining pattern, compatible with indirect myc up-regulation. |
| Treatment | Complete therapeutic data are available for one of the two ALL cases: treatment was started according to ALL-2009 protocol, containing Daunorubicin, Vincristine, and L-asparaginase. CNS prophylaxis therapy consisted of triple intrathecal treatments, whereas cranial irradiation was not used. The patient received allogeneic HSCT; conditioning regimen consisted of Melphalan and Fludarabine. |
| Prognosis | The risk associated with der(X)t(X;8)(q28;q11.2) is not well determined due to low number of cases. |
| Cytogenetics Morphological | Isolated derivative chromosome X was demonstrated in one ALL case (present case, 2016); in second one, the derivative chromosome X was combined with other recurrent chromosomal abnormalities (Kaleem et al, 2000). |
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GTG-banding showing the derivative X chromosome; FISH with whole painting probes showing two normal chromosomes 8 (green color) and the derivative der(X)t(X;8) (red and green colors). Multicolor banding of two normal chromosomes 8 and the derivative X chromosome. |
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| Probes | Whole chromosome painting (WCP X, WCP8), mBAND 8 (Metasystems, Germany). |
| Additional anomalies | Found in association with t(9;22)(q34;q11), t(8;14)(q11.2;q32) and add(17)(p13) in one ALL case (Kaleem et al,2000). |
