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2.
Cells ; 10(1)2021 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-33435150

RESUMEN

Chronic myeloid leukemia (CML) has been a "model disease" with a long history. Beginning with the first discovery of leukemia and the description of the Philadelphia Chromosome and ending with the current goal of achieving treatment-free remission after targeted therapies, we describe here the journey of CML, focusing on molecular pathways relating to signaling, metabolism and the bone marrow microenvironment. We highlight current strategies for combination therapies aimed at eradicating the CML stem cell; hopefully the final destination of this long voyage.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Modelos Biológicos , Epigénesis Genética , Historia del Siglo XX , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Terapia Molecular Dirigida , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Microambiente Tumoral/genética
3.
Br J Haematol ; 191(4): 521-526, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33190253

RESUMEN

Over the past 60 years, haematologists and scientists from the United Kingdom, notably John Goldman and Tessa Holyoake, have punched above their weight in changing chronic myeloid leukaemia (CML) from an incurable and invariably fatal disease for all, to a chronic condition where over 90% have normal life expectancy. As a result, it is now difficult to power a worthwhile phase 3 study for newly diagnosed patients. Nevertheless, important clinical questions remain.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Reino Unido/epidemiología
5.
Eur J Haematol ; 97(2): 145-54, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26519944

RESUMEN

OBJECTIVE: To assess the impact and results of treatment of CML in the general population, we conducted a population-based, nationwide study on 3585 CML patients diagnosed between 1989 and 2012 in the Netherlands. METHODS: Patient demographics were obtained from the Netherlands Cancer Registry. Information on age, gender, year of diagnosis, first treatment, and date of death were recorded. Overall survival (OS) was adjusted for death rates in the normal population. RESULTS: Incidence in males decreased slightly from 1.2 per 100.000 person years (PY) in 1989-2000 to 0.9 in 2001-2012. For females, incidence remained stable with 0.7 per 100.000 PY in both periods. Incidence was age dependent and highest in males in the last decades of life. Treatment before 2000 mainly consisted of chemotherapy, while after 2007 TKI use was 88%. Five-year relative survival was only 36% before the introduction of TKIs but significantly increased to 79% after the introduction of TKI. CONCLUSIONS: This study gives insight into CML incidence, treatment, and survival in routine care in the Netherlands. Although OS improved since the introduction of TKIs, there is still room for further improvement.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Antineoplásicos/uso terapéutico , Femenino , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Incidencia , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Países Bajos/epidemiología , Vigilancia de la Población , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del Tratamiento
6.
Bull Acad Natl Med ; 199(4-5): 717-28, 2015.
Artículo en Francés | MEDLINE | ID: mdl-27509687

RESUMEN

The hematological disorder Béla Bartók suffered during his exile in the United States and that led to his death has long remained mysterious, as well as the lung disease that accompanied it. The present historical evocation offers us the opportunity to explain the remarkable biological and therapeutic advances obtained in the field of chronic myelocytic leukemia during the last decades.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Personajes , Resultado Fatal , Historia del Siglo XX , Humanos , Hungría , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Enfermedades Pulmonares/etiología , Masculino , Música/historia , Síndromes Paraneoplásicos/diagnóstico , Estados Unidos
7.
Eur J Haematol ; 94(6): 540-5, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25315799

RESUMEN

BACKGROUND: Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are highly treatable conditions occurring primarily in older patients. Lower survival among older people has been reported in both conditions, but newer treatments may change both the overall survival rate and the relative risk associated with aging. Here, we examine survival for patients with CLL and CML in the United States (US) and England. METHODS: Patients with CLL and CML were identified from the Surveillance, Epidemiology, and End Results (US) and National Cancer Registry (England). Five-year relative survival was calculated by major age group. Excess hazard ratios (EHR) by age were calculated for each condition, and multivariable analysis was performed to adjust for the following potential confounders: gender, race or ethnic group (US only), period of diagnosis, and a measure of socioeconomic deprivation (England only). RESULTS: Five-year relative survival increased for both CLL and CML in both England and the US between 1996-2000 and 2006-2010. However, relative age-related disparities persisted. For CLL, the EHR for death was 9.44 (7.84-11.36) in the US and 6.14 (5.65-6.68) in England for ages 85+ compared to ages 55-64. For CML, the EHR was 3.52 (3.17-3.90) in the US and 4.54 (4.13-4.98) in England for ages 75+ compared to ages 45-64. CONCLUSIONS: Survival improved for patients with chronic leukemias in the early 21st century. However, age-related disparities persist, despite clinical trial evidence that treatment in older adults with chronic leukemia can be safe and effective. Further research to determine the reasons for the lower survival in older patients and greater awareness of this problem may improve survival for older patients with chronic leukemia.


Asunto(s)
Disparidades en Atención de Salud , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/historia , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Masculino , Persona de Mediana Edad , Sistema de Registros , Programa de VERF , Reino Unido/epidemiología , Estados Unidos/epidemiología , Adulto Joven
9.
Bull Cancer ; 101(1): 56-67, 2014 Jan 01.
Artículo en Francés | MEDLINE | ID: mdl-24491668

RESUMEN

During two centuries, advances in medicine and medical research have helped to understand the pathophysiology of chronic myelogenous leukemia (CML). This hematologic malignancy is a unique model of oncogenesis where a single molecular hit, causing cell proliferation and survival, was identified. The chromosomal abnormality first highlighted by P. Nowell and D. Hungerford in 1960, and characterized as the reciprocal translocation t(9;22)(q34;q11), the Philadelphia chromosome, discovered in leukemic cells, by J. Rowley in 1973. At the end of the 20th century, the contribution of molecular biology techniques was crucial by the discovery of the BCR-ABL1 hybrid oncogene derived from the t(9;22), responsible for the translation of an aberrant protein tyrosine kinase. This BCR-ABL1 kinase deregulates signaling pathways that control normal cell cycle and survival in primitive hematopoietic cells and is thus responsible for malignant cell accumulation observed in CML. It was then only necessary to develop a targeted treatment adapted to this molecular hit. Recently, tyrosine kinase inhibitors, by their specific inhibitory activity of BCR-ABL, have revolutionized the treatment of CML, allowing rates of haematological, cytogenetic and molecular responses never seen to date, and has significantly improved the overall survival and the quality of life of patients.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Arsénico/historia , Arsénico/uso terapéutico , Trasplante de Médula Ósea/historia , Proteínas de Fusión bcr-abl/genética , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Terapia Molecular Dirigida/historia , Terapia Molecular Dirigida/métodos , Cromosoma Filadelfia , Radioterapia , Translocación Genética
11.
Leuk Lymphoma ; 54(7): 1411-7, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23121646

RESUMEN

The use of interferon-α and allogeneic stem cell transplant and more recently of tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with chronic myeloid leukemia (CML). We performed a population-based study of CML to evaluate relative survival (RS) trend by treatment eras. All instances of CML diagnosed between 1975 and 2009 reported in the Surveillance, Epidemiology and End Results databases were reviewed. The incidence of CML was 1.75/100 000 persons per year and increased with age. The incidence was highest in Detroit and lowest among Asians. The 5-year RS ratios increased from 0.26 in patients diagnosed in 1975-1989 to 0.36 in 1990-2000 and 0.56 in 2001-2009. There was a significant improvement in 5-year RS ratios in the 2005-2009 calendar period compared to the 2001-2004 period (p < 0.05), corresponding to the introduction of second-generation TKIs. Age was the most important prognostic factor for RS, but the improvement in 5-year RS ratios was observed in all age groups except the group aged < 15 years (p > 0.05), including adolescents and young adults and elderly patient groups. There are ethnic and geographic variations in the incidence of CML. The RS improved with each treatment era, with the greatest improvement in all age groups occurring during the TKI era.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Incidencia , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Masculino , Persona de Mediana Edad , Programa de VERF , Análisis de Supervivencia , Estados Unidos/epidemiología , Estados Unidos/etnología , Adulto Joven
14.
Cancer Genet ; 204(4): 171-9, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21536234

RESUMEN

This report summarizes highlights of the Philadelphia Chromosome Symposium: Past, Present and Future, held September 28, 2010, to commemorate the 50th anniversary of the discovery of the Philadelphia chromosome. The symposium sessions included presentations by investigators who made seminal contributions concerning the discovery and molecular characterization of the Ph chromosome and others who developed a highly successful therapy based on the specific molecular alteration observed in chronic myeloid leukemia. Additional presentations highlighted future opportunities for the design of molecularly targeted therapies for various types of cancer. Also included here are reminiscences connected with the discovery of the Ph chromosome by David Hungerford and Peter Nowell, the discovery that the abnormality arises from a chromosomal translocation, by Janet Rowley, and the cloning of the 9;22 translocation breakpoints by Nora Heisterkamp, John Groffen, and colleagues.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Cromosoma Filadelfia , Antineoplásicos/uso terapéutico , Benzamidas , Clonación Molecular , Citogenética/historia , Citogenética/métodos , Citogenética/tendencias , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Translocación Genética
15.
Semin Hematol ; 47(4): 302-11, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20875546

RESUMEN

Patients with splenomegaly and abnormally high leukocyte counts were first recognized in France, Germany, and Scotland in the 1840s. The only well-documented therapy in the 19th century was use of arsenic in one or other form, which did undoubtedly reduce the leukocyte count but probably did little or nothing to prolong life. These early cases were probably examples of chronic myeloid leukemia (CML) (then called chronic granulocytic leukemia). In the 20th century important steps in unraveling the pathogenesis of CML were the discovery of the Philadelphia chromosome in 1960, and of the (9;22) translocation in 1973. There followed definition of the breakpoint cluster region on chromosome 22 in 1984 and the demonstration of the BCR-ABL transcript in CML in 1985. In the first half of the 20th century patients were treated predominantly with radiotherapy, and later on with busulfan, hydroxycarbamide, or interferon-alfa (IFN-α). From 1980 onwards allogeneic stem cell transplantation (SCT) became the treatment of choice for eligible patients. The era of tyrosine kinase inhibitors (TKI) began in 1998 and today the use of the original TKI, imatinib, has replaced SCT as initial therapy for patients who present with CML in chronic phase.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Antineoplásicos/historia , Antineoplásicos/uso terapéutico , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Trasplante de Células Madre , Trasplante Homólogo
16.
Cell ; 138(6): 1051-4, 2009 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-19766556

RESUMEN

This year the Lasker DeBakey Clinical Research Award will be shared by Brian Druker, Nicholas Lydon, and Charles Sawyers for their development of a targeted molecular therapy for treating chronic myeloid leukemia. Their work demonstrated the ability of drugs directed against cancer-causing oncogenes to turn a rapidly fatal malignancy into a manageable chronic disease.


Asunto(s)
Distinciones y Premios , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Protocolos Antineoplásicos , Benzamidas , Ensayos Clínicos Fase I como Asunto , Historia del Siglo XXI , Mesilato de Imatinib , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico
17.
Adler Mus Bull ; 35(1): 3-13, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20052806

RESUMEN

Arsenicals have been used since ancient Greek and Roman civilizations and in the Far East as part of traditional Chinese medicine. In Western countries, they became a therapeutic mainstay for various ailments and malignancies in the 19th and early 20th centuries. Fowler's potassium bicarbonate-based solution of arsenic trioxide (As2O3)solution was the main treatment of chronic myeloid leukaemia until the 1930s. After a decline in the use of arsenic during the mid-20th century, arsenic trioxide was reintroduced as an anticancer agent after reports emerged from China of the success of an arsenic trioxide-containing herbal mixture for the treatment of acute promyelocytic leukaemia. Arsenic trioxide was first purified and used in controlled studies in China in the 1970s.Subsequently, randomised clinical trials performed in the United States led to FDA approval of arsenic trioxide in the treatment of patients with relapsed or refractory acute promyelocytic leukaemia.


Asunto(s)
Arsénico , Ensayos Clínicos como Asunto , Materia Medica , Medicina Tradicional , Venenos , Terapéutica , Arsénico/historia , Intoxicación por Arsénico/etnología , Intoxicación por Arsénico/historia , Ensayos Clínicos como Asunto/historia , Medicina de Hierbas/educación , Medicina de Hierbas/historia , Historia del Siglo XIX , Historia del Siglo XX , Leucemia Mielógena Crónica BCR-ABL Positiva/etnología , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Materia Medica/historia , Medicina Tradicional/economía , Medicina Tradicional/historia , Medicina Tradicional/psicología , Preparaciones de Plantas/historia , Venenos/historia , Terapéutica/historia , Terapéutica/psicología
18.
Blood ; 112(13): 4808-17, 2008 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-19064740

RESUMEN

Throughout its history, chronic myeloid leukemia (CML) has set precedents for cancer research and therapy. These range from the identification of the first specific chromosomal abnormality associated with cancer to the development of imatinib as a specific, targeted therapy for the disease. The successful development of imatinib as a therapeutic agent for CML can be attributed directly to decades of scientific discoveries. These discoveries determined that the BCR-ABL tyrosine kinase is the critical pathogenetic event in CML and an ideal target for therapy. This was confirmed in clinical trials of imatinib, with imatinib significantly improving the long-term survival of patients with CML. Continuing in this tradition of scientific discoveries leading to improved therapies, the understanding of resistance to imatinib has rapidly led to strategies to circumvent resistance. Continued studies of hematologic malignancies will allow this paradigm of targeting molecular pathogenetic events to be applied to many additional hematologic cancers.


Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Cromosoma Filadelfia , Benzamidas , Investigación Biomédica/historia , Sistemas de Liberación de Medicamentos/historia , Sistemas de Liberación de Medicamentos/métodos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/historia , Cromosoma Filadelfia/efectos de los fármacos , Piperazinas/historia , Piperazinas/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirimidinas/historia , Pirimidinas/farmacología
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