Is the primary event in radiation-induced chronic myelogenous leukemia the induction of the t(9;22) translocation?

Holmberg, M.

doi:10.1016/0145-2126(92)90134-s

Cited by 18 publications

(9 citation statements)

References 11 publications

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“…The results of this study showed a corresponding increase in the diagnosis of CML to the radiation dose [ 35 ]. A calculation of 0.0007/Gy has been created to represent the risk of acquiring the translocation (9:22) after exposure to radiation [ 36 ]. Because people have been living longer as a result of chemotherapy and radiation treatment, it must be considered that an increase in reported secondary malignancies may be simply due to an increased lifespan.…”

Section: Discussionmentioning

confidence: 99%

Unusual Case of Simultaneous Presentation of Plasma Cell Myeloma, Chronic Myelogenous Leukemia, and a Jak2 Positive Myeloproliferative Disorder

Maerki

Katava

Siegel

et al. 2014

Case Reports in Hematology

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Background. Multiple articles discuss the rare incidence and potential causes of second hematologic disorders arising after treatment of Chronic Myelogenous Leukemia (CML), leading to the theory of imatinib, the current treatment regimen for CML, as a possible trigger for the development of secondary neoplasms. Our case eliminates the possibility of imatinib as the sole cause since our patient received a diagnosis of simultaneous plasma cell myeloma, CML, and a Jak2 mutation positive myeloproliferative disorder (MPD) arising de novo, prior to any treatment. We will further investigate into alternative theories as potential causes for multiple hematopathologic disorders. Case Report. There are currently no reported cases with the diagnosis of simultaneous plasma cell myeloma, chronic myelogenous leukemia, and Jak2 positive myeloproliferative disorder. We present a case of a 77-year-old male who was discovered to have these three concurring hematopathologic diagnoses. Our review of the literature includes a look at potential associations linking the three coexisting hematologic entities. Conclusion. The mechanism resulting in simultaneous malignancies is most likely multifactorial and potentially includes factors specific to the host, continuous stimulation of the immune system, previous chemotherapy or radiation, a potential common pluripotent stem cell, or, lastly, preexisting myeloma which may increase the susceptibility of additional malignancies.

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Section: Discussionmentioning

confidence: 99%

Unusual Case of Simultaneous Presentation of Plasma Cell Myeloma, Chronic Myelogenous Leukemia, and a Jak2 Positive Myeloproliferative Disorder

Maerki

Katava

Siegel

et al. 2014

Case Reports in Hematology

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“…The leukemogenic basis for the radiation-related CML was demonstrated by Holmberg [13], who hypothesized that the t(9;22) translocation was the primary event in radiation-induced CML. In fact, unlike most chemicals, Rx can induce in G0 cells, such as the pluripotent hematopoietic stem cells, reciprocal transloca-tions, whose frequency has been calculated in human lymphocytes irradiated in vitro [9].…”

Section: Discussionmentioning

confidence: 99%

Chronic myelogenous leukemia and exposure to ionizing radiation — a retrospective study of 443 patients

et al. 1995

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Exposure to ionizing radiations (Rx) has been implicated as a causative factor of chronic myelogenous leukemia (CML). We performed a retrospective study of 443 consecutive CML patients, looking for a history of significant exposure to Rx, and evaluated the clinical and hematological characteristics in order to find any difference between radiation-related CML patients and those with de novo CML. We identified 406 patients without known exposure to mutagens (group I) and 37 patients with prior significant exposure to Rx (group II). In comparison to patients of group I, those of group II showed particular clinical and hematological features: significantly lower incidence of bulky splenomegaly (p < 0.05) and hyperleukocytosis (WBC > 100 x 10(9)/l; p < 0.05); significantly higher incidence of anemia (Hb < 10 g/dl; p < 0.01). Patients with radiation-related CML had a significantly better survival than those with de novo CML (median survival 61 months vs 42 months; p < 0.05). In conclusion, this study of a large cohort of CML patients indicates that the subgroup of patients with a history of significant exposure to ionizing radiation has particular clinical and hematological features at onset (lower tumor burden, higher frequency of anemia) and a better survival.

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“…At a dose of 1 Gy the frequency of reciprocal translocations in human lymphocytes in vitro has been estimated to be 0.1/cell [36]. The probability of induction of a t(9;22), as in Ph c CML, has been calculated to be on the order of 7!10 -12 per Gy per cell [48]. While a dose-response relationship for the development of leukemia was shown in atomic bomb survivors, it was not as clearly demonstrated in patients treated with RT or radionuclides for cancer or other diseases.…”

Section: The Role Of Irradiation and Radiotherapy In The Development mentioning

confidence: 99%

Treatment-related chronic myelogenous leukemia

Waller

Fetscher

Lange

1999

Annals of Hematology

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Treatment-related (Tr) AML and MDS after chemotherapy, radiotherapy, or the combination of both have been well characterized. However, tr-CML seems to differ from these better-known entities in frequency, clinical course, and prognosis. Tr-CML cannot be distinguished from de novo CML cytogenetically, and, in contrast to tr-AML and tr-MDS, typical chromosomal aberrations related to tr-CML have not been described. Treatment-related CML is a late effect of cytotoxic or immunosuppressive therapy which might be increasingly recognized due to a higher number of patients treated with intensive therapy regimens. We review here the available data on incidence of tr-CML as well as the affected individual's characteristics with regard to different treatment options in malignant and nonmalignant diseases.

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Is the primary event in radiation-induced chronic myelogenous leukemia the induction of the t(9;22) translocation?

Cited by 18 publications

References 11 publications

Unusual Case of Simultaneous Presentation of Plasma Cell Myeloma, Chronic Myelogenous Leukemia, and a Jak2 Positive Myeloproliferative Disorder

Unusual Case of Simultaneous Presentation of Plasma Cell Myeloma, Chronic Myelogenous Leukemia, and a Jak2 Positive Myeloproliferative Disorder

Chronic myelogenous leukemia and exposure to ionizing radiation — a retrospective study of 443 patients

Treatment-related chronic myelogenous leukemia

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