TY - JOUR
T1 - Chronic myeloid leukemia (CML) evolves from Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) with unexpected frequency
AU - Hochman, Michael J.
AU - Smith, B. Douglas
AU - Karantanos, Theodoros
AU - Braunstein, Evan M.
AU - Gojo, Ivana
AU - Jain, Tania
AU - Streiff, Michael B.
AU - Moliterno, Alison R.
AU - DeZern, Amy E.
N1 - Publisher Copyright:
© 2022, Japanese Society of Hematology.
PY - 2023/3
Y1 - 2023/3
N2 - Myeloproliferative neoplasms (MPN) are chronic clonal disorders characterized by overproduction of myeloid-lineage blood cells and potential risk of evolution to acute myeloid leukemia (AML). Chronic myeloid leukemia (CML) is distinct from other MPNs in that its pathophysiology stems from the BCR-ABL fusion protein of the Philadelphia chromosome (Ph +). Though there are known cases of Ph- and Ph + MPNs coexisting in a single patient, overall prevalence has never been quantified in a prospective cohort. Here, we review our center’s MPN registry, which shows 0.6% of Ph- MPN patients later developed CML. This development occurred no less than 10 and up to 36 years after Ph- MPN diagnosis. This rate of chronic transformation exceeds what is expected, as the incidence of CML in the United States is 2 per 100,000 people-years. The probability of this CML case rate in an average-risk population is less than 0.001%, suggesting there are shared risk factors between Ph- and Ph + MPNs. We speculate that these risk factors may include exposures, genetic predispositions, or be inherent to disease biology. Abrupt-onset leukocytosis heralded post-MPN CML in all cases here and suggests this salient clinical feature should trigger hematologists to consider this diagnosis and perform appropriate testing.
AB - Myeloproliferative neoplasms (MPN) are chronic clonal disorders characterized by overproduction of myeloid-lineage blood cells and potential risk of evolution to acute myeloid leukemia (AML). Chronic myeloid leukemia (CML) is distinct from other MPNs in that its pathophysiology stems from the BCR-ABL fusion protein of the Philadelphia chromosome (Ph +). Though there are known cases of Ph- and Ph + MPNs coexisting in a single patient, overall prevalence has never been quantified in a prospective cohort. Here, we review our center’s MPN registry, which shows 0.6% of Ph- MPN patients later developed CML. This development occurred no less than 10 and up to 36 years after Ph- MPN diagnosis. This rate of chronic transformation exceeds what is expected, as the incidence of CML in the United States is 2 per 100,000 people-years. The probability of this CML case rate in an average-risk population is less than 0.001%, suggesting there are shared risk factors between Ph- and Ph + MPNs. We speculate that these risk factors may include exposures, genetic predispositions, or be inherent to disease biology. Abrupt-onset leukocytosis heralded post-MPN CML in all cases here and suggests this salient clinical feature should trigger hematologists to consider this diagnosis and perform appropriate testing.
KW - Cancer epidemiology
KW - Chronic myeloid leukemia
KW - JAK2
KW - Myeloproliferative neoplasms
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U2 - 10.1007/s12185-022-03463-0
DO - 10.1007/s12185-022-03463-0
M3 - Article
C2 - 36181657
AN - SCOPUS:85139239545
SN - 0925-5710
VL - 117
SP - 456
EP - 462
JO - International journal of hematology
JF - International journal of hematology
IS - 3
ER -