Leucemia mieloide crónica

Hurtado et al, Cancerología 2 (2007): 137-147

Chronic Myeloid Leukemia
Current Concepts in
Physiopathology
and Treatment
Rafael Hurtado Monroy1 , Pablo Vargas Viveros1 y Jorge Cortes Franco2
1 Hospital Ángeles del Pedregal, México
2 Professor of Medicine. Department of Leukemia, Unit 428: The University of Texas: M.D. Anderson Cancer Center.

Resumen•

Abstract•

La leucemiamieloide crónica (LMC) es una enfermedad mieloproliferativa, clonal y heterogenea, que
se origina por una transformación noeoplásica de la
célula hematopoyética primitiva. La presencia de la
traslocación balanceada t(9;22) (q34;q1 conocida
1),
como cromosoma Philadelphia (Ph) es la base para
el diagnóstico y tratamiento de la enfermedad. En
este artículo se describen las vías de señalizaciónafectadas por esta traslocación, así como las también
se analizan las bases de leucemogénesis. De igual
forma, se revisan los avances en la terapia blanco,
incluyendo al mesilato de imatinib, así como a los inhibidores de tirocino cinasas de segunda generación,
que han modificado de manera importante, no sólo
la historia natural de la enfermedad, sino también
la calidad de vida,principalmente de los pacientes
en fase crónica. El mejor entendimiento de las bases
moleculares y progresión de la LMC será importante
para el desarrollo futuro de nuevas moléculas que
permitan vencer la resistencia en estos pacientes.

HRONIC MYELOID LEUKEMIA (CML)
is a heterogenous clonal myeloproliferative disorder, which occurs from the
neoplastic transformation of the primitive hematopoieticstem cell. The presence of a balanced translocation t(9;22) (q34;q1 known as the
1),
Philadelphia (ph) chromosome is the basis of the
diagnosis and the hallmark of the treatment. A description of the signaling pathways affected by this
translocation, as well as the basis for leukemogenesis
is analyzed. In the same way, novel targeted therapy
are reviewed, including imatinib mesylate(Glivec®),as well as the second generation tyrosine kinase inhibitors, which have changed importantly, not only
the natural history of this disease, but also the quality of life, mainly in patients with early chronic phase
disease. A better understanding of the molecular
basis of CML progression will be very important for
the future and the development of new molecules
to overcome resistance.

Keywords: Leucemia Mieloide Crónica, Inhibidores
de Tirocinocinasa, Mesilato de Imatinib

Palabras Clave: Chronic Myeloid Leukemia, Tyrosine Kinase Inhibitors, Imatinib Mesylate.

C

Correspondencia a:
Rafael Hurtado Monroy
Hospital Ángeles del Pedregal, México
Camino a Santa Teresa 1055-243.
Col. Héroes de Padierna.
C.P. 10700. México D.F.
e-Mail: rafahurtado@prodigy.net.mx

137Introduction•
Chronic myeloid leukemia (CML), a clonal myeloproliferative disorder, has its origin in the neoplastic transformation of primitive hematopoietic
stem cells (1). The presence of a balanced translocation between the long arms of chromosomes
9 and 22, t(9;22) (q34;q11), known as the Philadelphia (ph) chromosome (2), is the basis of the
diagnosis and a hallmark for treatment.proteins have unregulated constitutive tyrosine
kinase activity, which also induce the activation
of a number of intracellular signaling pathways,
such as proliferation, adherence, and apoptosis
(13). Bcr-Abl is essential for cell transformation
and allows the assembly of phosphorylated substrates in multiprotein complexes that transmit
mitogenic and antiapoptotic signals (14).

The diseaseis heterogeneous in its presentation and clinical course, prognosis and therapy,
which has changed during the last seven years
(3, 4). The availability of more effective therapy
with Imatinib mesylate (Glivec®) has changed
the natural history of the disease, and today
represents the major success in the era of target-directed cancer chemotherapy. In this article
the new knowledge of the...