Biology and Diagnosis of Acute Leukemias

**13**

**Chapter 2**

**Abstract**

*Ashraf Abdullah Saad*

can be easily mistaken for JMML.

**1. Introduction**

Juvenile Myelomonocytic

Myeloid Leukemia (AML)

Leukemia (JMML): A Mimicker

Juvenile myelomonocytic leukemia (JMML) is the most confusing mimicker of *KMT2A*-rearranged acute myeloid leukemia (AML). Clinical presentation, age of susceptibility (infancy or early childhood) and abnormal monocytosis are common clinical features. To complicate matters, JMML morphologically resemble acute myelomonocytic leukemia (AML M4) and distinction must be made based on accurate blast and promonocyte counts. As treatment significantly varies, AML/JMML overlap can lead to catastrophic consequences that can be avoided by timely management. Therefore, meticulous knowledge of JMML is essential to treat patients with hematologic malignancies. The pathognomic feature of JMML is increased infiltration of the peripheral blood, bone marrow, and viscera by abnormal myelomonocytic cells. Molecular diagnostics has generated substantial dividends in dissecting the genetic basis of JMML. We can now molecularly confirm the diagnosis of JMML in approximately over 90% of patients who harbor driver mutations in *KRAS, NRAS, PTPN11, NF1*, or *CBL* genes. The presence of monosomy 7 is a classic feature of JMML that can support the diagnosis in many cases. On the other hand, cytogenetics and Fluorescence in situ hybridization analysis (FISH) are indispensable to differentiate *KMT2A*-rearranged AML from JMML. In particular, AML with t(9;11) is associated with monocytic features that

**Keywords:** JMML, *KMT2A*, DNA hypermethylation, p-STAT5, azacitidine

JMML is a rare aggressive clonal hematopoietic neoplasm of infancy and early childhood that combines excessive proliferation of the granulocytic and monocytic lineages with dysplasia making JMML analogous to chronic myelomonocytic leukemia (CMML). Therefore, the current WHO classification of myeloid neoplasms and acute leukemia envisages JMML as an overlap myeloproliferative/ myelodysplastic neoplasm. The diagnosis of JMML is mainly based on the clinical presentation in combination with morphology of the peripheral blood smears and the molecular analysis of leukemic cells. The peripheral blood and bone marrow of

of *KMT2A*-Rearranged Acute
